Maintenance of genomic stability stability cell cycle checkpoint gene. Medical search. Frequent questions

In this article, we will take a closer look at the RAD50 gene and its importance, learn about the various types of RAD50 gene mutations, and explore the key risk factors and symptoms associated with these mutations . (tangut.net)
RAD50 gene mutations can lead to a variety of defects that disrupt the normal functioning of the MRN complex, thus affecting DNA repair, recombination, and genome stability. (tangut.net)
Changes or abnormalities in this gene can occur as a result of genetic inheritance, exposure to toxins or radiation, or through spontaneous mutations. (tangut.net)
3. Frameshift Mutations: These mutations occur when the addition or deletion of nucleotides in the RAD50 gene shifts the reading frame of the genetic code, leading to an altered protein structure and function. (tangut.net)
5. Splice-Site Mutations: These mutations affect the way in which the RAD50 gene is processed during mRNA production, leading to altered protein synthesis. (tangut.net)
RAD50 gene mutations can increase the risk of various cancers and other health issues. (tangut.net)
Individuals with a positive family history of cancer or other genetic disorders are at higher risk of carrying RAD50 gene mutations. (tangut.net)
Exposure to environmental toxins or radiation may also increase the likelihood of gene mutations. (tangut.net)
RAD50 gene mutations can be diagnosed through genetic testing, which involves analyzing DNA samples for abnormalities in the RAD50 gene sequence. (tangut.net)
Treatment options for RAD50 gene mutations depend on the specific type of mutation and associated symptoms. (tangut.net)
Loss of functional DNA repair genes is a key feature of base pair mutations found in hereditary cancers. (medium.com)
DNA damage predisposes normal cells and transforms into cancer cell mutations with expression of antigenic determinants related to cancer cell life cycle initiation and survival. (medium.com)
DUSP4 alterations lead to hyperactivation of MAPK signaling in many cancers, including breast cancer, which often harbor mutations in cell cycle checkpoint genes, particularly in TP53. (biomedcentral.com)
This study identifies a novel mechanism for breast tumorigenesis implicating Dusp4 loss and p53 mutations in cellular acquisition of Dbf4 upregulation as a driver of cellular replication and cell cycle checkpoint escape. (biomedcentral.com)
We find that together with loss-of-function mutations in p53 and, to some degree, potentiated by cMyc overexpression, Dusp4 deletion aids in cell cycle checkpoint escape while simultaneously potentiating hallmarks of replicative stress, including multinucleation and Chk1 phosphorylation. (biomedcentral.com)
Heterozygous germ line mutations in the genes coding for components of MutSα (MSH2 and MSH6) and MutLα (MLH1 and PMS2) have been recognized as major causes of this syndrome ( 1 ). (aacrjournals.org)
These alterations can take the form of epigenetic modifications, point mutations, translocations, amplifications or deletions and modify gene functions in ways that deregulate cellular signalling pathways leading to the cancer phenotype. (bmj.com)
These modifications comprise point mutations, changes in the gene copy number, complete rearrangements, and epigenetic alterations [ 3 ] . (encyclopedia.pub)
PARP inhibitors (PARPis) can induce synthetic lethality in cancer cells with preexistent defects in the homologous recombination (HR) repair pathway, such as deleterious mutations of the breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) suppressor genes [ 7 ] [ 8 ] . (encyclopedia.pub)
Unraveling of GBM biology found mutations [ 1 ] in other genes that also result in BRCAness and confer sensitivity to PARPi treatment. (encyclopedia.pub)
Our studies are focused on targets of the checkpoint pathways involving the tumor suppressors and the checkpoint kinases CHK1 and CHK2, of which mutations are associated with human cancers. (sinica.edu.tw)
Mutations and gene amplifications that confer drug resistance emerge frequently during chemotherapy, but their mechanism and timing are poorly understood. (babraham.ac.uk)
Melanoma in particular exhibits a high incidence of activating BRAF and NRAS mutations and such cells are addicted to the activity of these mutant oncoproteins. (babraham.ac.uk)
A direct link between DNA DSBs, genomic instability, and cancer is evidenced the fact that many cancer-predisposition syndromes in humans characterized by genomic instability are caused by mutations in DSB-responsive genes ( 16 , 17 ). (amegroups.org)
However, cancer cells overcome these controls, in particular by acquiring genetic mutations leading to the activation of oncogenes (pten, myc) or loss of tumor suppressors (p53) [ 1 ]. (hindawi.com)
A total of 1021 genes underwent target panel sequencing reveal that SETD2 mutations were associated with a higher TMB. (biomedcentral.com)
Furthermore, we find a high rate of JMJD1B mutations in cancer patients, and a correlation with genomic instability. (biomedcentral.com)
Although genomic alterations have been extensively characterized in AML [ 1 ], little is known about the determining events that favor the accumulation of mutations and the progression from the pre-leukemic to leukemic stage. (oncotarget.com)
[ 2 ] Mutations in the NBN ( NBS1) gene located in band 8q21 are responsible for Nijmegen breakage syndrome. (medscape.com)

When this gene is mutated or altered, it can lead to genomic instability, cancer and various other health issues. (tangut.net)
DSBs are cytotoxic lesions, which if left unrepaired could lead to genomic instability, cancer and even cell death. (springeropen.com)
Defects in DNA damage repair can lead to genomic instability and cancer development. (villajoyosacf.info)

In the DNA damage pathways, the INO80 subfamily aids in repair, recombination, and cell cycle regulation. (wikipedia.org)
The MRN complex plays a critical role in maintaining the stability of genetic material, as it is involved in crucial DNA repair pathways and cell cycle checkpoints. (tangut.net)
Many exogenous and endogenous triggers for senescence have been recognized to act via genomic or epigenomic pathways. (elsevierpure.com)
Therefore, there are multiple conserved pathways within cells that respond to such errors by recruiting DNA repair processes or initiating apoptosis. (medium.com)
The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
In this review, we showcase recent studies on the splicing and AS of key genes in metabolic pathways in the liver, the effect of metabolic signals on the spliceosome, and therapeutic intervention points based on RNA splicing. (imperial.ac.uk)
These signaling pathways are disrupted in GBM, and despite the accumulation of DNA damage, cancerous cells will thrive, maintaining survival and pathological cell division [ 2 ] [ 4 ] . (encyclopedia.pub)
This killing process occurs only if two molecular pathways are simultaneously deficient in one cell, whereas the isolated defect is innocuous [ 6 ] . (encyclopedia.pub)
The E3 ubiquitin ligase RAD18 is well known for the maintenance of genome stability and cell survival through many DNA damage response (DDR) pathways such as translesion DNA synthesis (TLS) and homologous recombination repair (HRR) [ 4 , 5 ]. (nature.com)
Lipids, amino acids, and nucleotides necessary for the biosynthesis of the daughter cells are mostly provided by intermediate metabolites of these pathways. (hindawi.com)
To prevent aberrant cell proliferation, these pathways are tightly regulated. (hindawi.com)
Cells have evolved with conserved recombination mediated genome editing pathways as a mean for repairing DSBs and restarting replication forks, thus allowing genome duplication to continue [ 8 ]. (springeropen.com)
What pathways are this gene/protein implicaed in? (cancerindex.org)
The main role of p53 as a tumor suppressor relies on its transcriptional activity to regulate target genes in a variety of biological pathways (Sullivan et al. (villajoyosacf.info)

consequently cells have evolved a variety of mechanisms to repair double-strand breaks (DSBs). (brandeis.edu)
Through detailed characterization of fundamental molecular mechanisms of normal and perturbed cells, the theme strives to unravel information that increases the understanding of various diseases such as cancer and neurodegenerative, cardiovascular and inflammatory disorders. (ki.se)
The stem cell and developmental biology program at CMB is engaged in a broad range of basic research aimed at understanding the molecular mechanisms underlying diverse aspects of embryonic development and tissue regeneration. (ki.se)
Genomic stability relies around the precise execution of DNA replication, chromosome segregation, DNA repair and genomic monitoring mechanisms, and their integration with cell cycle progression and also other processes. (rockinhibitor.com)
Surveillance is a key control integrated in many multi-functions and mechanisms including DNA damage checkpoint, DNA repair machinery and mitotic checkpoint. (medium.com)
I will be elaborating on the stages of DNA surveillance and repair and demonstrate how defects in the regulation of any of these mechanisms often results in genomic instability, which predisposes the cell to malignant transformation. (medium.com)
It is known to halt cancer cell proliferation and the propagation of DNA damage and can also initiate DNA repair mechanisms. (medium.com)
In addition to its role in NHEJ, Ku70/80 is also required for telomere length maintenance [9] and other important cellular mechanisms. (termedia.pl)
While the contribution of these mechanisms to cell and tissue identity is widely accepted, their role in physiological and pathological contexts within tissues is just beginning to be appreciated. (imperial.ac.uk)
Cells have various mechanisms to restore length (TELOMERE HOMEOSTASIS. (lookformedical.com)
In this paper, we describe the metabolic changes as well as the mechanisms of resistance to apoptosis occurring in cancer cells and cancer stem cells, underlying the connection between these two processes. (hindawi.com)
Research in G&E labs is broadly focused on the fundamental genetic, epigenetic, and genomic mechanisms that control cell growth and differentiation, and that cause cancer and other human diseases. (uth.edu)
Homologous recombination' is one of the main mechanisms used by cells to repair DNA double-strand breaks. (elifesciences.org)
The disorders are characterized by a defect in DNA repair mechanisms or genomic instability, and patients with these disorders show increased predisposition to cancer. (medscape.com)

The senescence cascade and the cell-cycle checkpoints that dictate the progression and maintenance of senescence are important in all types of gastrointestinal cancers, including pancreatic, liver, gastric, colon, and esophageal cancers. (elsevierpure.com)
The encoded protein plays a role in many cellular processes including cell cycle progression, DNA repair and apoptosis by regulating the activity of protein phosphatase 1. (nih.gov)
Cancer is a multi-factorial process, however, cancer cell mutation load, tumor initiation and progression through genomic instability has obvious relation to loss of gene function as seen in mutator phenotypes and relation to oncogene initiation and induced DNA replication stress. (medium.com)
This feature of cancer cell mutation and tumor progression has been studied for many decades as a hallmark feature, however, there is much uncertainty in its relation to early process or final transformation process in cancer evolution. (medium.com)
The first is a stochastic model of the progression of cell cycle states, which is applied to experimental data for two synchronized isogenic MMR + and MMR − colon cancer cell lines treated with and without IUdR. (aacrjournals.org)
Furthermore, we find that SET8 interacts with proliferating cell nuclear antigen through a conserved motif, and SET8 is required for DNA replication fork progression. (rupress.org)
Telomere shortening is involved in the progression of CELL AGING. (lookformedical.com)
Accumulating evidence shows that cancer stem cells are key drivers of tumor formation, progression, and recurrence. (hindawi.com)
Molecular portraits of cell cycle checkpoint kinases in cancer evolution, progression, and treatment responsiveness. (uc.edu)
Once activated by DSBs, ATM/Tel1 and ATR/Mec1 promote DSB repair, delay cell cycle progression or trigger the elimination of genetically unstable cells by inducing cell death. (elifesciences.org)
Finally, CAFs promote cancer progression and act in cancer cell drug resistance. (spandidos-publications.com)
For instance, DNA replication and DNA damage checkpoints delay cell cycle progression until each chromosome is fully replicated and physically intact. (rupress.org)
By exogenously modulating its activity, we demonstrate that PP1α is required to maintain CHK1 in a dephosphorylated state and, more importantly, that it is responsible for the accelerated replication fork progression in Spi1/PU.1-overexpressing cells. (oncotarget.com)
Thus, the safeguarding of genetic stability is a major defense against tumor initiation and progression. (oncotarget.com)

2, 3 Genomic alterations in BRCA1 are found in 40-50% of families with a high incidence of breast cancer (six or more cases), and in a majority (75-80%) of the families that display both breast and ovarian cancers. (bmj.com)
The regulation of DNA repair by the cell cycle is largely the result of chromatin alterations that happen through DNA replication, compression, and dissociation that permit cells to divide effectively [8]. (rockinhibitor.com)
These genetic alterations result in either activation or inactivation of specific gene functions that contribute to the process of carcinogenesis. (bmj.com)
The present review summarizes the recent achievements in understanding the gene profiles of CAFs and pays special attention to their possible epigenetic alterations. (spandidos-publications.com)
A total of 7 possible genetic alterations and epigenetic changes in CAFs are discussed, including gene differential expression, karyotype analysis, gene copy number variation, loss of heterozygosis, allelic imbalance, microsatellite instability, post‑transcriptional control and DNA methylation. (spandidos-publications.com)
It is widely recognized that the accumulation of various harmful genetic alterations in normal cells may induce malignant cancer cells ( 1 ). (spandidos-publications.com)
Genetic alterations include genetic mutation, gene copy number variation (CNV), loss of heterozygosity (LOH), allelic imbalance (AI) and microsatellite instability (MSI). (spandidos-publications.com)

8- 10 In attempts to identify new breast and ovarian cancer susceptibility genes, much research has focused on BRCA1 associated proteins. (bmj.com)

Yao Y, Dai W. Genomic Instability and Cancer. (medium.com)

p53 represses the promoter of Polo-like kinase 1, whereas Polo-like kinase 1 inhibits p53 and its family members p63 and p73 in cancer cells lacking functional p53. (oncotarget.com)
Thus, inactive p53 is not associated with a susceptible cytotoxicity of Polo-like kinase 1 inhibition and could rather foster the induction of polyploidy/aneuploidy in surviving cells. (oncotarget.com)
In addition, compared to the mono-treatment, combination of Polo-like kinase 1 inhibition with anti-mitotic or DNA damaging agents boosts more severe mitotic defects, effectually triggers apoptosis and strongly inhibits proliferation of cancer cells with functional p53. (oncotarget.com)
In this regard, restoration of p53 in tumor cells with loss or mutation of p53 will reinforce the cytotoxicity of combined Polo-like kinase 1 therapy and provide a proficient strategy for combating relapse and metastasis of cancer. (oncotarget.com)
Checkpoint kinase 2 (CHEK2), a cell cycle checkpoint regulator gene, codes for a kinase protein activated in response to radiation and other agents that cause breaks in the DNA. (termedia.pl)
DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key component of the non-homologous end-joining (NHEJ) pathway, is involved in DNA double-strand break repair, immunocompetence, genomic integrity, and epidermal growth factor receptor signaling. (amegroups.org)
Emerging evidence indicate that the mammalian checkpoint kinase ATM induces transcriptional silencing in cis to DNA double-strand breaks (DSBs) through a poorly understood mechanism. (elifesciences.org)
Here, we demonstrate that the S phase checkpoint protein CHK1 is maintained in a low phosphorylation state in Spi1/PU.1-overexpressing cells and provide evidence that this is not due to negative control of its primary kinase ATR. (oncotarget.com)

The RAD50 gene codes for a protein that is part of a highly conserved protein complex called Mre11-Rad50-NBS1 (MRN). (tangut.net)
The RAD50 protein, in particular, plays a crucial role in homologous recombination, which is an essential mechanism for genome maintenance and repair. (tangut.net)
The key interests lie within the field of genome integrity and variation, cell division, regulation of gene expression, protein turnover and signal transduction. (ki.se)
This gene encodes a protein phosphatase 1 binding protein. (nih.gov)
MYC dephosphorylation by the PP1/PNUTS phosphatase complex regulates chromatin binding and protein stability. (nih.gov)
The Rep proteins and the plasmid-encoded Raf protein also regulate plasmid gene transcription. (bvsalud.org)
This includes gene, protein and metabolic networks, cellular architecture and intracellular dynamics, cell communication and motility, cell division and differentiation, tissue formation and organogenesis, tissue and organ functions, changes in population characteristics as a consequence of interaction of organisms with their physical environment, with individuals of their own species, and with organisms of other species. (nih.gov)
from Int J Paediatr Dent 2000 Dec;10(4):328-34) The X-linked form is also known as Zinsser-Cole-Engman syndrome and involves the gene which encodes a highly conserved protein called dyskerin. (lookformedical.com)
A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the CELL CYCLE. (lookformedical.com)
The BRCA2 R3052W mutated protein exacerbates genome instability, is unable to rescue homology-directed repair, and fails to complement cell survival following exposure to PARP inhibitors and crosslinking drugs. (frontiersin.org)
DNA nuclease/helicase 2 (DNA2), a multi-functional protein protecting the high fidelity of genomic transmission, plays critical roles in DNA replication and repair processes. (longevityfacts.com)
Microtubule-associated protein MAP1LC3C regulates lysosomal exocytosis and induces zinc reprogramming in renal cancer cells. (uc.edu)
Of the 31 genes, the 21 upregulated genes were primarily associated with cell paracrine and intracellular signaling, transcription regulation and cell adhesion and migration, and their transcriptional products included transforming growth factor-β2 (TGF-β2), insulin-like growth factor-binding protein 2 and transcriptional factor AP-2α/γ ( 11 ). (spandidos-publications.com)
The protein encoded by this gene belongs to the pyridine nucleotide-disulfide oxidoreductase family, and is a member of the thioredoxin (Trx) system. (cancerindex.org)
What does this gene/protein do? (cancerindex.org)
We found that TRIM13 mRNA and protein expression was reduced in NSCLC tissues and cell lines in comparison to paired non-cancerous tissues and a human normal bronchial epithelial cell line, respectively. (cancerindex.org)
In this review, we describe the effects of MDM2 on genomic instability, the role of MDM2 in p53 release and binding of DNA repair proteins to inhibit repair, and the regulatory network of MDM2, including its transcriptional modifications, protein stability, and localization. (villajoyosacf.info)
We therefore asked what role JMJD1B plays in newly synthesized histone maturation by exploiting the knockdown of JMJD1B by treating HeLa cells with siRNA against JMJD1B (siJMJD1B) and observed the reduction of both JMJD1B protein on cytosolic extracts (Fig. 1 b) and mRNA levels (Fig. 1 c) 72 h after the treatment. (biomedcentral.com)

Combined treatment with selumetinib and a dose of palbociclib sufficient to reinforce G1 arrest in selumetinib-sensitive cells, but not to impair proliferation of resistant cells, delays the emergence of resistant colonies, meaning that escape from G1 arrest is critical in the formation of resistant clones. (babraham.ac.uk)
However, a function for SET8 in mammalian cell proliferation has not been determined. (rupress.org)
We show that small interfering RNA inhibition of SET8 expression leads to decreased cell proliferation and accumulation of cells in S phase. (rupress.org)
Genes that suppress carcinogenesis have been classified as gatekeepers that regulate cellular proliferation and cell death and as caretakers that are primarily encode DNA repair proteins required for the maintenance of genome integrity ( 15 ). (amegroups.org)
High expression of RAD18 facilitated a highly stem-cell phenotype through the Hippo/YAP pathway, which supports the proliferation of TNBC. (nature.com)
Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. (lookformedical.com)
Cell proliferation involves the replication of all cellular contents with the required energy for this to happen. (hindawi.com)
This activation is necessary for both cell proliferation as well as glucose uptake and use. (hindawi.com)
CAFs provide cancer cells with nutrition and promote the proliferation, invasion and metastasis of cells ( 6 - 9 ). (spandidos-publications.com)
TRIM13 inhibited cell proliferation and induced cell apoptosis by regulating NF-κB pathway in non-small-cell lung carcinoma cells. (cancerindex.org)
Overexpression of TRIM13 in NCI-H1975 and SPC-A-1 cells hampered cell proliferation. (cancerindex.org)
The oncoprotein murine double minute 2 (MDM2) promotes cell survival, proliferation, invasion, and therapeutic resistance in many types of cancer. (villajoyosacf.info)
AP4 presumably contributes to the phenotype of cancer cells by activating or repressing genes that harbor CAGCTG elements in their promoter regions, thereby controlling processes such as proliferation, metabolism, apoptosis, epithelial-mesenchymal transition (EMT) and metastasis [ 5 ]. (biomedcentral.com)

CMB is comprised of more than 30 independent research groups organized in three themes: Cell Biology, Developmental and Stem Cell Biology and Infection and Cancer. (ki.se)
Within the context of DNA double-strand breaks, MUS81 maintainshttp://jcancer.orgJournal of Cancer 2019, Vol.genome stability by forming a heterodimer with Eme1/Mms4 and resolving the Holliday junction (HJ) [6]. (rockinhibitor.com)
Genomic instability is a hallmark of cancer cells primarily effecting cell division. (medium.com)
MSI is also observed in non small cell lung cancer but the prognosis with this pattern is poor. (medium.com)
Chromosomal instability is a manifest of genome instability with complexities that require careful attention to individual gene control features specific to the cancer cell mutation, tumor microenvironment and surrounding moiety. (medium.com)
Using a genetically engineered mouse model, we generated mammary-specific Dusp4 -deleted primary epithelial cells to investigate the necessary conditions in which DUSP4 loss may drive breast cancer oncogenesis. (biomedcentral.com)
Given the previously reported role of DUSP4 as a p53 target, a potential cell cycle checkpoint, and in mediating senescence downstream of replication stress, we hypothesized that DUSP4 may be a critical oncogenic driver in breast cancer. (biomedcentral.com)
Scientists working in basic, translational, and clinical cancer metabolism research are invited to join the Academy in New York on April 17th to discuss the intersection between cell signaling and metabolism. (nyas.org)
Previous studies in our laboratory have described increased and preferential radiosensitization of mismatch repair-deficient (MMR − ) HCT116 colon cancer cells with 5-iododeoxyuridine (IUdR). (aacrjournals.org)
DNA repair targeted therapy, which kills cancer cells preventing DNA repair [1-3]. (termedia.pl)
These inhibitors inhibit NHEJ-catalyzed DSB repair and sensitize in vitro cancer cells to DSB-inducing agents. (termedia.pl)
CHEK2 is not only a breast cancer susceptibility gene but also a multi-organ cancer susceptibility gene [15]. (termedia.pl)
We performed whole exome sequencing (WES) of 156 cervical cancer tissues to assess genomic features related to platinum-based chemoresistance. (biomedcentral.com)
Knockdown of SETD8 increased the responsiveness of cervical cancer cells to cisplatin treatment. (biomedcentral.com)
While genomic instability contributes to the poor prognosis for GBM patients [ 5 ] , the damaged DNA offers a target for pharmacological approaches that induce cancer cell death by a mechanism called synthetic lethality. (encyclopedia.pub)
By using molecular approaches, cell-based and mouse models, we hope to uncover novel tumor suppressors and their modes of action, through which potential therapeutics could be devised to improve cancer treatment. (sinica.edu.tw)
These studies unveiled a novel function of DNA-PKcs in safeguarding the genome integrity and cancer suppression as chromosomal instability (CIN) plays an important role in cancer development and is a hallmark of cancer cells ( 14 ). (amegroups.org)
Carcinogenesis is a multi-step process wherein abrogation of multiple cancer susceptibility genes leads to cancer development. (amegroups.org)
However, the mechanism through which RAD18 influences triple-negative breast cancer (TNBC), especially the interaction between tumor cells and the tumor microenvironment, remains elusive. (nature.com)
In contrast to normal cells, most cancer cells predominantly produce energy by a high rate of glycolysis followed by lactate fermentation, even in the presence of oxygen, a less efficient metabolism compared to a low rate of glycolysis followed by mitochondrial oxidation of pyruvate [ 2 ]. (hindawi.com)
In contrast, cancer cells shift their metabolism toward lactate production even in the presence of oxygen [ 4 ], partly through genetic modifications that stabilize the transcription factor Hypoxia Inducible Factor (HIF) involved in the adaptation of the cells to hypoxia, under nonhypoxic conditions as well as generating an adaptive response to the hypoxic microenvironment (Figure 1 ). (hindawi.com)
Metabolic adaptations of cancer cells. (hindawi.com)
Glucose and glutamine are the 2 major substrates used by cancer cells. (hindawi.com)
As detailed on our website, the G&E Program tackles foundational questions in development and disease that can be grouped into five research areas: epigenetics, developmental genetics, human genetics, cancer genetics, and genome maintenance and repair. (uth.edu)
However, erroneous repair of DSBs can lead to chromosomal rearrangements and loss of heterozygosity, which in turn can also cause cancer and cell death. (springeropen.com)
We also elaborate on the potential of targeting HR genes for cancer therapy and anticancer strategies. (springeropen.com)
In the past decade, the use of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of a variety of tumors, including lung cancer, melanoma, colorectal cancer, and renal cell carcinoma [ 1 , 2 ]. (biomedcentral.com)
DNA double-strand breaks (DSBs) are particularly dangerous for cells, since their inefficient or inaccurate repair can result in deletions and chromosomal translocations that can lead to cancer and/or severe developmental abnormalities in humans. (elifesciences.org)
CAFs maintain their phenotype for numerous passages during culture in vitro without exposure to cancer cells, while NFs cannot be infinitely proliferous like cancer cells ( 10 ). (spandidos-publications.com)
The use of cell therapies, drivers of immune response, and trends in immunotherapy were the focus of the Immunotherapy Bridge (November 30th-December 1st, 2022), organized by the Fondazione Melanoma Onlus, Naples, Italy, in collaboration with the Society for Immunotherapy of Cancer. (biomedcentral.com)
The clinical success of immune checkpoint inhibitors has dramatically changed outcomes for patients across cancer types. (biomedcentral.com)
The study and/or manipulation of administered cells can potentially result in identification of the exact cell subpopulations and effector functions required for cancer regression in vivo. (biomedcentral.com)
Clinical activity of TIL therapy has also been reported in other cancer types, including human papillomavirus-associated cancers, cholangiocarcinoma, non-small-cell lung cancer (NSCLC), and triple-negative breast cancer (TNBC). (biomedcentral.com)
Genomic instability is a hallmark of cancer and is regulated by the balance between DNA damage and repair (Aguilera and Garcia-Muse, 2013). (villajoyosacf.info)
Here, we set out to determine the relevance of AP4 in human colorectal cancer (CRC) cells. (biomedcentral.com)
Cancer is the result of a multi-step process driven by the progressive accumulation of genetic and epigenetic changes in several genes that alter the activity and/or expression of their products, partners and targets. (oncotarget.com)
This is a Phase IB/II multi-cohort study designed to evaluate the efficacy and safety of targeted agents with or without cancer immune checkpoint therapy with atezolizumab in participant with recurrent and/or persistent endometrial cancer. (ucbraid.org)
Table 1 provides a summary outline of the gene symbols, chromosomal locations, radiation sensitivity characteristics, immunodeficiencies, chromosome breakage characteristics, and major cancer risk for each of these disorders. (medscape.com)

Approximately 5-10% of all breast and ovarian cancers are thought to arise from a hereditary predisposition to the disease, 1 BRCA1 and BRCA2 being the most important susceptibility genes. (bmj.com)

In addition to this function, the INO80 subfamily plays a role in transcriptional regulation and genomic recombination. (wikipedia.org)
PARP is a family of enzymes that comprises 17 members with different functions, such as maintenance of genomic stability, transcriptional regulation, and cell death [ 16 ] [ 17 ] . (encyclopedia.pub)

Recombination between homologous sequences is a fundamentally important process both in meiosis and in mitotic cells. (brandeis.edu)
To this end we have expressed the site-specific HO endonuclease in meiotic cells so that we can compare recombination events at the same loci where we have used HO to stimulate recombination in mitotic cells. (brandeis.edu)
Thus, the products of chromosome replication (sister chromatids) generated during S-phase must be identified over time until mitosis when sisters associate with the mitotic spindle and segregate away from each other into the newly forming daughter cells. (rupress.org)

The SOSS complex associates with DNA lesions and influences diverse endpoints in the cellular DNA damage response including cell-cycle checkpoint activation, recombinational repair and maintenance of genomic stability. (thermofisher.com)
Cellular senescence is a biologically irreversible state of cell-growth arrest that occurs following either a replicative or an oncogenic stimulus. (elsevierpure.com)
6, 7 BRCA1 interacts with a variety of proteins and is involved in multiple cellular processes including DNA repair, transcription, and checkpoint control. (bmj.com)
In addition, the effects of reduced Bard1 expression have been studied in murine mammary epithelial cell cultures, where it was associated with complex cellular changes suggestive of a premalignant phenotype. (bmj.com)
We found that Dusp4 loss alone is insufficient in mediating tumorigenesis, but alternatively converges with loss in Trp53 and MYC amplification to induce tumorigenesis primarily through chromosome 5 amplification, which specifically upregulates Dbf4 , a cell cycle gene that promotes cellular replication by mediating cell cycle checkpoint escape. (biomedcentral.com)
Plk3 is expressed throughout the cell cycle and involved in cellular response to DNA damage [ 9 ]. (oncotarget.com)
Yu-Che Cheng, Sheau-Yann Shieh* Determination of CHK1 Cellular Localization by Immunofluorescence Microscopy Cell Cycle Checkpoints. (sinica.edu.tw)
Thermal stability assays show that ERKi do not destabilise ERK2 (or ERK1) in vitro, suggesting that ERK2 turnover is a cellular consequence of ERKi binding. (babraham.ac.uk)
For example, RAD18 plays a vital role in regulating the DNA stability of embryonic stem cells and cellular homeostasis in highly prolific cells [ 6 ]. (nature.com)
In normal cells, glucose participates in cellular energy production through glycolysis as well as through its complete catabolism via the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). (hindawi.com)
(B) Western blot of total cellular lysates from DLD-1 BRCA2 −/− cells stably transfected with full-length BRCA2 cDNA constructs: BRCA2 Wild Type (WT) and BRCA2 R3052W (1 and 2 correspond to two independent clones). (frontiersin.org)
(F) Western blot of total cellular lysates from DLD-1 parental cells (these cells express a wild-type allele of BRCA2) stably transfected with R3052W (3 and 5 correspond to two independent clones) full-length 2XMBP-BRCA2 cDNA constructs. (frontiersin.org)
S. mansoni USPs showed changes in expression levels for different life cycle stages indicating their involvement in cellular processes required for S. mansoni development. (biomedcentral.com)
Inactivation of AP4 in CRC cell lines resulted in increased spontaneous and c-MYC-induced DNA damage, chromosomal instability (CIN) and cellular senescence. (biomedcentral.com)
We investigated its cellular localization and found it in both cytosolic and nuclear extracts derived from HeLa cells (Fig. 1 a). (biomedcentral.com)
In 1998, on the basis of cellular phenotypes and the results of somatic cell complementation studies suggesting genetic heterogeneity, Jaspers et al proposed the term A-T variants for diseases in this group of patients. (medscape.com)

The most common stimulus for senescence is progressive loss of telomeric DNA, which results in the loss of chromosomal stability and eventual unregulated growth and malignancy. (elsevierpure.com)
Senescence is activated through an interaction between the p16 and p53 tumor-suppressor genes. (elsevierpure.com)
Senescent cells can be identified in vitro because they express senescence-associated β-galactosidase, a marker of increased lysosomal activity. (elsevierpure.com)
MSC use frequently requires in vitro expansion, thus exposing cells to replicative senescence. (encyclopedia.pub)
Activated p53 induces programmed cell death (apoptosis) or senescence as a last attempt to avoid possible malignant transformation when the damage is too severe and beyond repair. (medium.com)
Interestingly, replication stress in Brca2-null cells activates p53 and the expression of its target genes, including senescence-inducing Ink4/Arf. (biomedcentral.com)
When damaged DNA cannot be repaired, a functional DDR machinery triggers a signaling cascade, leading to cell senescence or apoptosis. (encyclopedia.pub)
Conversely, intact damage can lead to transcription and replication arrest, leading to cell death and senescence (Hoeijmakers, 2009). (villajoyosacf.info)
Inhibition of miR-22-3p or ectopic MDC1 expression reversed the increased senescence, DNA damage, CIN and defective HR observed in AP4 -deficient CRC cells. (biomedcentral.com)

In response to endogenous and exogenous insults, malignant cells mostly have an intensive DNA repair capacity that allows them to proliferate and survive. (nature.com)
The risk is increased 1000-fold for squamous cell carcinoma, basal cell carcinoma, malignant melanoma, and fibrosarcoma and is increased 10-fold to 20-fold for other tumors. (medscape.com)

The SET domain containing 2 histone lysine methyltransferase ( SETD2) gene encodes the functional domain of an enzyme that trimethylates histone H3 at lysine 36 (H3K36me3), which mediates MMR in a way that removes lesions associated with a persistently open chromatin structure in early replication, and preferentially safeguards active transcripts during replication by recruiting hMutSa which can quickly identify the mismatch to initiate the MMR reaction [ 15 , 16 ]. (biomedcentral.com)
The prostaglandin-endoperoxide synthase 2 gene (PTGS2), which encodes cyclooxygenase-2, was found to upregulate the expression of TGF-β2 ( 14 ). (spandidos-publications.com)
This gene encodes an ubiquitously expressed, cytosolic form of TrxR, which functions as a homodimer containing FAD, and selenocysteine (Sec) at the active site. (cancerindex.org)
AP4 (TFAP4) encodes a basic helix-loop-helix leucine zipper (bHLH-LZ) transcription factor and is a direct target gene of the oncogenic transcription factor c-MYC. (biomedcentral.com)
AP4 -deficient cells displayed increased expression of the long non-coding RNA MIR22HG, which encodes miR-22-3p and was directly repressed by AP4. (biomedcentral.com)

This has led to the need for new immunotherapy-based approaches, including adoptive cell transfer (ACT), therapeutic vaccines, and novel immune checkpoint inhibitors. (biomedcentral.com)

Due to the low abundance of MSCs in human adult tissues (about 1/10 6 cells in adult bone marrow and 1/10 3-4 cells in adipose tissue and umbilical cord) [ 16 ] , frequently ex-vivo expansion precedes therapeutic administration, to obtain a clinically relevant number of cells. (encyclopedia.pub)
Key areas of investigation are the identification and functional characterization of stem cell niches in developing tissues and adult organs. (ki.se)
Deletion (loss of heterozygosity), mutation, and methylation-induced gene promoter silencing of MSH2 and MLH1 have been reported as probable reasons for somatic inactivation of a MSH2 or MLH1 wild-type allele, leading to sporadic tumor development in multiple tissues, including gastrointestinal, gynecologic, and genitourinary ( 2 - 5 ). (aacrjournals.org)
Development of new or improved laboratory/experimental techniques, instruments, or supporting software that measure the location and dynamics of molecules in situ, and organelles, cells, or tissues on the nanometer and micrometer length scales. (nih.gov)
Mechanochemical Principles of Spatial and Temporal Patterns in Cells and Tissues. (mpi-cbg.de)
Patterns are ubiquitous in living systems and underlie the dynamic organization of cells, tissues, and embryos. (mpi-cbg.de)

Plk1 inhibitors target all rapidly dividing cells irrespective of tumor cells or non-transformed normal but proliferating cells. (oncotarget.com)
Upon treatment with Plk1 inhibitors, p53 in tumor cells is activated and induces strong apoptosis, whereas tumor cells with inactive p53 arrest in mitosis with DNA damage. (oncotarget.com)
This has resulted in the development of additional immunotherapy-based approaches, including adoptive cell transfer (ACT), therapeutic vaccines, and inhibitors of other immune checkpoints. (biomedcentral.com)

SET8 depletion causes DNA damage specifically during replication, which induces a Chk1-mediated S-phase checkpoint. (rupress.org)

The proteins involved in homologous recombination have to work around other processes that go on inside the nucleus, such as the transcription of DNA in genes into RNA molecules. (elifesciences.org)
Previous research has reported that forming a double-strand break in the DNA reduces the levels of transcription for the genes that surround the break, but it was not clear how this occurred. (elifesciences.org)
In mammalian cells, inhibiting the transcription of genes around a double-strand DNA break depends on a signaling pathway that is activated whenever DNA damage is detected. (elifesciences.org)
One of the next challenges will be to see if the resection process makes any contribution to changes in the transcription of genes that surround a double-strand break in mammals as well. (elifesciences.org)
We previously showed that constitutive overexpression of the oncogenic transcription factor Spi1/PU.1 leads to pre-leukemic cells that have a shortened S phase duration with an increased replication fork speed and increased mutability in the absence of DNA breaks. (oncotarget.com)

29 Moreover, a recent study in mice showed that loss of Bard1 results in early embryonic lethality and chromosomal instability, indicating a role of Bard1 in maintenance of genomic integrity. (bmj.com)
Genomic stability is essential in cell maintenance and integrity. (medium.com)
Hence, although the repair of DSBs is crucial for the maintenance of genome integrity the process of repair need to be well regulated and closely monitored. (springeropen.com)
Regardless of how DSBs are formed, faithful repair of these breaks are absolutely essential for maintenance of genome integrity. (springeropen.com)
DNA damage in the maintenance of genome integrity and control of the MDM2-p53 axis. (villajoyosacf.info)

It is also involved in cell cycle arrest and apoptosis [17]. (termedia.pl)
The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS. (lookformedical.com)
A successful therapy must therefore eliminate these cells known to be highly resistant to apoptosis. (hindawi.com)
TRIM13-induced NSCLC cell apoptosis was attenuated by a caspase-3 inhibitor Ac-DEVD-CHO, suggesting that TRIM13 induced cell apoptosis partially through a caspase-3-dependent pathway. (cancerindex.org)

Deletion or mutation of genes coding for Ku70 or Ku80 proteins results in a highly radiosensitive phenotype [10]. (termedia.pl)
Transferred T cells that persist in the blood and form memory have a phenotype consistent with a less differentiated state (CD27/CD28/IL-7 receptor-α) [ 3 ]. (biomedcentral.com)

11 Both proteins possess an N-terminal RING finger motif and two BRCA1 C-terminal (BRCT) domains present in numerous proteins involved in DNA repair and cell cycle regulation. (bmj.com)
We have shown that this regulation involves the action of a small Recombination Enhancer (RE) sequence that enables a donor on the left chromosome arm to recombine preferentially in MATa cells. (brandeis.edu)
As a structure-specific endonuclease, MUS81 is involved in cell cycle regulation and regulates the DNA damage repair approach. (rockinhibitor.com)
Here, we demonstrate that GFI1 is required in T cells for the regulation of key DNA damage signaling and repair proteins. (bvsalud.org)
Immunofluorescence, chromosome and micronuclei enumeration, MTT and colony formation assays were used to determine the effects of AP4 inactivation and target gene regulation on chromosomal instability (CIN) and drug sensitivity. (biomedcentral.com)

This is not a single gene event, there are multiple genes that initiate, control and regulate tumor suppressor function and cell division. (medium.com)
It is a tumor suppressor gene, involved in DNA DSB repair through the process of homologous recombination [16]. (termedia.pl)
The tumor suppressor gene p53 regulates cell cycle arrest to allow time for DNA repair. (villajoyosacf.info)

SETD2 protects against genomic instability via maintenance of homologous recombination repair (HRR) and mismatch repair (MMR) in neoplastic cells. (biomedcentral.com)

The BRCA2 R3052W mutation fails to complement chemotherapeutic sensitivity and homology-directed repair functions in BRCA2 knockout cells. (frontiersin.org)

A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. (lookformedical.com)
Failure to repair DSBs can lead to unwanted consequences, such as loss of genetic information, chromosomal rearrangements and even cell death. (springeropen.com)
Further investigations revealed that in vitro cells derived from patients with Nijmegen breakage syndrome display characteristic abnormalities similar to those observed in ataxia-telangiectasia (A-T) , including spontaneous chromosomal instability, sensitivity to ionizing radiation (IR), and radioresistant DNA synthesis (RDS). (medscape.com)
In culture, cells from affected individuals exhibit elevated rates of chromosomal breakage or instability, leading to chromosomal rearrangements. (medscape.com)

The use of cell therapies, drivers of immune response, and trends in immunotherapy were the focus of the Immunotherapy Bridge (November 30th-December 1st, 2022). (biomedcentral.com)

These helicases contribute to genome maintenance and are unique to the INO80 subfamily of chromatin remodeling complexes. (wikipedia.org)
Experiments with Ku70/80 knocked out mice indicate that NHEJ is important for genome maintenance [8]. (termedia.pl)
Our main goals are to decipher the molecular basis of checkpoint control by these proteins, their functional relationship with DNA repair and genome maintenance, and the impacts on tumorigenesis. (sinica.edu.tw)

Basic genetic and molecular biology methodologies are combined with complementary bioinformatic and genome-wide approaches, allowing investigation global molecular changes in cells in various differentiation processes. (ki.se)
The yeast 2-µm plasmid is a remarkable genetic parasite, managing efficient maintenance at high-copy number with minimal impact on the host. (bvsalud.org)
ERKi treatment of cells drives the poly-ubiquitylation and proteasome-dependent turnover of ERK2 and pharmacological or genetic inhibition of Cullin-RING E3 ligases prevents this. (babraham.ac.uk)
RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (lookformedical.com)
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. (lookformedical.com)
Genetic ablation of diabetes-associated gene Ccdc92 reduces obesity and insulin resistance in mice. (uc.edu)

RAD50 is a human gene that plays a pivotal role in DNA repair, recombination and genome stability. (tangut.net)
The RAD50 gene plays a critical role in DNA repair, recombination, and genome stability. (tangut.net)
Using synchronized cells undergoing recombination that is initiated at a specific site on a chromosome by an inducible endonuclease, we use physical monitoring techniques (Southern blots, PCR analysis) to follow the sequence of molecular events that occur in real time. (brandeis.edu)
DNA-PKcs and the NHEJ pathway are also essential for V(D)J recombination during T and B cell lymphocyte development. (amegroups.org)

Here a DSB at the MAT locus is created by a site specific HO endonuclease, which we can induce synchronously in a large population of cells. (brandeis.edu)
MDM2 can inhibit both p53 and NBS1 to regulate multiple physiological processes and/or induce genomic instability, in which ATM plays a central phosphorylation regulatory role. (villajoyosacf.info)

By contrast, the 10 downregulated genes were primarily associated with epithelial membrane proteins ( 11 ). (spandidos-publications.com)

We are also interested in gene targeting methods and in figuring out why these types of gene replacement and modification are quite inefficient, even in yeast. (brandeis.edu)
This research aims at characterizing molecules and signals involved in controlling the undifferentiated state and self-renewal capacity of stem cells, and to develop methods to direct the differentiation of stem cells into clinically relevant cell types. (ki.se)

Additionally, RAD18 functions beyond DNA repair and may regulate many other key biological processes, such as chromatin strengthening, cell survival/death, stemness, and differentiation. (nature.com)

DNA double strand breaks (DSBs) result as a consequence of the disassembly of the DNA double helix leading to the disruption of the stability of the genome. (springeropen.com)

MSCs represent a lifelong reservoir for the generation of somatic cells and for cell replacement. (encyclopedia.pub)

Mesenchymal stem/stromal cells (MSCs) are a reservoir for tissue homeostasis and repair that age during organismal aging. (encyclopedia.pub)
Maintenance of genomic stability is crucial for standard development, cell homeostasis and tumor suppression [7]. (rockinhibitor.com)

Five members of the Plk family have been discovered in humans and these serine/threonine kinases have emerged as key players by performing crucial functions in the cell cycle, DNA damage response and neuron biology [ 2 - 6 ]. (oncotarget.com)

There is also a need for rational combinations beyond interleukin (IL)-2 and programmed death (PD)-1/ cytotoxic T-lymphocyte-associated antigen (CTLA)-4 immune checkpoint blockade and to combat exhaustion and restore costimulatory functions, e.g., with gene-engineered or pharmacologic agent-treated TILs. (biomedcentral.com)

Cells grown in vitro from neoplastic tissue. (lookformedical.com)

Maintaining a proper supply of soluble histones throughout the cell cycle is important to ensure chromatin and genome stability. (biomedcentral.com)

Overexpression of R3052W in DLD1 parental BRCA2 wild-type cells confers sensitivity to MMC DNA damage. (frontiersin.org)

Selumetinib causes long-term G1 arrest accompanied by reduced expression of DNA replication and repair genes, but cells stochastically re-enter the cell cycle during treatment despite continued repression of pERK1/2. (babraham.ac.uk)

Non-homologous end joining (NHEJ), which does not depend upon sequence homology, is the key repair pathway during the G0/G1 stages of the cell cycle [ 10 ]. (springeropen.com)

11 The functionally important BARD1/BRCA1 heterodimer formation is mediated by the RING finger motifs and has also been shown to markedly increase the stability of both proteins. (bmj.com)
Cell lysates had been resolved by SDS-PAGE, and proteins had been electro transferred to polyvinylidene fluoride membranes (Millipore, USA). (rockinhibitor.com)
Equal partitioning of the plasmid upon host cell division requires plasmid proteins Rep1 and Rep2 and the plasmid STB locus. (bvsalud.org)
Genome stability is maintained by intricate networks of cell cycle checkpoint proteins. (sinica.edu.tw)
Proteins in this class include those that perform functions such as telomere capping, telomere maintenance and telomere stabilization. (lookformedical.com)
Tripartite Motif Containing 13 (TRIM13), a member of TRIM proteins, is deleted in multiple tumor types, especially in B-cell chronic lymphocytic leukemia and multiple myeloma. (cancerindex.org)

The INO80 subfamily can activate the recruitment of replication checkpoint factors and can aid in the recovery from replicative stress on the DNA strand. (wikipedia.org)
Thus, determining how cells cope with replicative stress can help our understanding of oncogenesis and lead to the identification of new antitumor treatment targets. (oncotarget.com)

These cells possess both differentiation plasticity (stemness) and tissue supportive functions (stromalness) that can coexist and overlap, with differences depending on tissue source, donor characteristics, culture conditions and delivery strategies, leading to alternative best fittings for the term "stem" or "stromal" [ 7 ] . (encyclopedia.pub)

In addition, Gfi1b-DN mice exhibit an expansion of erythroid precursors indicative of a mildly abnormal erythropoiesis but without noticeable red blood cell defects. (bvsalud.org)
Infections in DNA repair defects may occur due to primary defects in T, B, or NK cells and other factors such as anatomic defects, neurologic disorders, or during chemotherapy. (mdpi.com)

Notably, we found that the expression of the CHK1 phosphatase PP1α is increased in Spi1/PU.1-overexpressing cells. (oncotarget.com)

The ATPase domain of the N-terminus functions in the identification of DNA damage and aids in the stability of telomeres. (wikipedia.org)
In addition cells have evolved a damage-sensing checkpoint system whereby the cells delay entry into mitosis until the break has been repaired. (brandeis.edu)
Specifically, the concepts of tumour heterogeneity, oncogene addiction, non-oncogene addiction, tumour initiating cells, tumour microenvironment, non-coding sequences and DNA damage response will be reviewed. (bmj.com)
In response to genotoxic stress, either extrinsic such as ionizing radiation-induced DNA breaks or intrinsic such as oxidative damage, a cascade of signaling events are initiated to arrest the cell cycle, eliminate damaged cells, or to repair the damage. (sinica.edu.tw)
Breaks that form across both strands in a DNA double helix are considered the most dangerous type of DNA damage, and can cause a cell to die or become cancerous if they are not repaired accurately. (elifesciences.org)
P53 deficiency results in reduced repair activity and decreased cell survival after UV-induced DNA damage, suggesting the involvement of p53 in nucleotide excision repair (NER) (Smith et al. (villajoyosacf.info)
Furthermore, Mediator of DNA damage Checkpoint 1 ( MDC1 ), a central component of the DNA damage response and a known target of miR-22-3p, displayed decreased expression in AP4 -deficient cells. (biomedcentral.com)

When the RAD50 gene is functioning properly, the MRN complex helps to detect and repair double-strand DNA breaks, which can occur naturally during cell replication or due to external factors such as radiation or exposure to certain chemicals. (tangut.net)

Cell functional assays, in vivo xenografts tumor growth experiments, and survival analysis were used to investigate the functional significance and mechanism of chemosensitization after SETD8 downregulation. (biomedcentral.com)

[ 1 ] These patients are at high risk for developing hematological malignancies in the first two decades of life, most commonly T-cell lymphoblastic malignancies and diffuse large B cell lymphoma. (medscape.com)

Nature Reviews Molecular Cell Biology. (wikipedia.org)
Thus the theme encloses expertise within bioinformatics, biophysics, biochemistry, molecular cell biology and genetics. (ki.se)

This phenomenon occurs as a response to the presence of premalignant cells and appears to be an important anticancer mechanism that keeps these transformed cells at bay. (elsevierpure.com)

The central aim of the research within the Cell Biology theme is to gain a deeper understanding of the biology of the eukaryotic cell. (ki.se)

Moreover, DNA2 potentially participates in controlling the cell cycle by repairing the DNA replication faults at main checkpoints. (longevityfacts.com)

Anatomy22

Organisms5

Diseases11

Chemicals and Drugs101

Analytical, Diagnostic and Therapeutic Techniques and Equipment28

Phenomena and Processes100

Disciplines and Occupations2

Information Science3

Health Care4

Mutations29

Lead to genomic instability3

Pathways14

Mechanisms14

Progression14

Alterations7

Breast and ovarian cancer susceptibility genes1

Instability and Cancer1

Kinase8

Protein18

Proliferation13

Cancer38

Susceptibility1

Transcriptional regulation2

Mitotic3

Cellular16

Senescence9

Malignant2

Encodes5

Immune checkpoint inhibitors1

Tissues6

Inhibitors3

Induces1

Transcription5

Integrity5

Apoptosis4

Phenotype2

Regulation5

Tumor suppressor3

Homologous recombination repair1

Mutation1

Chromosomal4

20221

Genome maintenance3

Genetic6

Recombination4

Induce2

Epithelial1

Methods2

Regulate1

DSBs1

Somatic1

Homeostasis2

Kinases1

Cytotoxic T lymphocyte-associat1

Vitro1

Chromatin1

BRCA21

Replication and repair1

Sequence1

Proteins6

Replicative stress2

Differentiation1

Defects2

CHK11

Damage7

Double-strand1

Functional1

Diffuse large B1

Molecular2

Mechanism1

Biology1

Participates1