Brca1 damage cell cycle checkpoint gene. Medical search. Frequent questions

Mutations in BReast CAncer 1 (BRCA1) and BReast CAncer 2 (BRCA2) are significantly related. (wikipedia.org)
The lifetime risk of a female developing breast and/or ovarian cancer increases if she inherits a harmful mutation of BRCA1 or BRCA2, but the severity depends on the type of mutation. (wikipedia.org)
Each year, about 3% of breast cancers and 10% of ovarian cancers result from inherited mutations in the BRCA1 and BRCA2 genes. (wikipedia.org)
It is estimated that less than 1% of the general population has a mutation in the BRCA1 or BRCA2 genes. (wikipedia.org)
Mutations in BRCA1 and BRCA2 are 10 times more common in Ashkenazi Jewish individuals. (wikipedia.org)
Genetic testing is available for testing mutations in BRCA1 and BRCA2. (wikipedia.org)
We investigated a panel of 34 known high/moderate-risk cancer genes, including 16 related to breast or ovarian cancer (BC/OC) genes, and 63 candidate genes to BC/OC in 192 clinically suspicious of hereditary breast/ovarian cancer (HBOC) Spanish families without pathogenic variants in BRCA1 or BRCA2 (BRCA1/2). (cancerindex.org)
It is currently estimated that 5 to 10% of all breast and ovarian cancer cases are inherited and the breast cancer susceptibility genes, BRCA1 and BRCA2, have been identified as being responsible for up to 21 to 40% of these cases. (biomedcentral.com)
Yale Cancer Center has an especially impressive armamentarium in the study of BRCA1 and BRCA2, proteins involved with DNA repair that, when mutated, can cause breast , ovarian , prostate , and pancreatic cancers. (yale.edu)
Both the BRCA1 and BRCA2 protein are involved in DNA repair," said Megan King , PhD , associate professor of cell biology and of molecular, cellular and development biology, and co-leader of the Radiobiology and Genome Integrity Research Program at Yale Cancer Center. (yale.edu)
That's important, because typically in clinical trials we lump together patients with BRCA1 and BRCA2 mutations. (yale.edu)
In collaboration with AstraZeneca, Jensen has focused on three BRCA2 reversion alleles, containing deletions in the BRCA2 gene that reactivate DNA repair functions, in tumor cell DNA from ovarian cancer patients who relapsed on a PARP inhibitor. (yale.edu)
Examples of these genes are BRCA1 and BRCA2 in breast and ovarian cancers. (hindawi.com)
Although inherited mutations in a small number of genes account for only about five to ten percent of women's cancers, by far the BRCA1 and BRCA2 gene mutations are the most common examples of this observation (50-70% of familial breast cancers) [ 2 ]. (hindawi.com)
Most cases of breast cancer do not 'run in families', but the well-known genes BRCA1 and BRCA2 can increase the risk of developing breast cancer (and also ovarian cancer). (biotopics.co.uk)
Most women have a 12% chance of developing breast cancer in their lifetime, and women with mutated BRCA1 or BRCA2 genes may have as much as an 80% chance, and they are more likely to develop it at an early age. (biotopics.co.uk)
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)
To date, inheritance of a mutant BRCA1 or BRCA2 gene is the best-established indicator of an increased risk of developing breast cancer. (jci.org)
Genetic testing for deleterious mutations in breast cancer 1, early onset gene ( BRCA1 ) and BRCA2 can provide key information to guide clinical decision making. (jci.org)
In the clinic, genetic testing for BRCA1 and BRCA2 mutations is offered to women in high-risk families and yields one of several possible results. (jci.org)
Homologous recombination (HR) is generally considered the most faithful DSB repair pathway, as it uses the intact sister chromatid as a donor, and it is highly dependent on breast cancer associated genes BRCA1 and BRCA2. (encyclopedia.pub)
Functional loss of both alleles of the breast cancer susceptibility gene, BRCA2, facilitates tumorigenesis. (ijbs.com)
Here, BRCA2 heterozygosity was mimicked in HT-29 colon cells by reducing levels of BRCA2 through stable RNA interference. (ijbs.com)
Interestingly, the growth rate of the mimicked BRCA2 heterozygous cell line was significantly lower than that of control cells. (ijbs.com)
Increased expression of p53 in the mimicked heterozygous cells was observed, perhaps in response to BRCA2 deficiency. (ijbs.com)
Levels of p27 were also found to be slightly increased in cells with reduced BRCA2, perhaps contributing to the slower growth rate. (ijbs.com)
Overall, these results suggest that tumors are unlikely to arise directly from BRCA2 heterozygous cells without other genetic events such as loss of the wild-type BRCA2 allele and/or loss of p53 function or other cell cycle inhibitors. (ijbs.com)
The majority of inherited breast and ovarian cancers are caused by germline mutations of the BRCA1 and BRCA2 genes [ 1 ]. (ijbs.com)
Loss of wild-type function of both BRCA2 alleles allows tumors to proliferate in affected individuals, classifying BRCA2 as a tumor suppressor gene [ 4 ]. (ijbs.com)
The human BRCA2 gene encodes a nuclear protein of 3,418 amino acids [ 5 ], and is believed to play a pivotal role in DNA damage repair [ 6 ]. (ijbs.com)
In support of this notion, cells lacking a functional BRCA2 gene show hypersensitivity to DNA damaging agents such as mitomycin C (MMC) and sensitivity to chemicals such as methyl methane sulfonate [ 10 ]. (ijbs.com)
In addition, cells with homozygous truncations in BRCA2 are genetically unstable [ 8 , 9 , 11 ] and are lacking in homology-directed DNA repair of chromosomal breaks [ 12 , 13 ]. (ijbs.com)
The effect of heterozygosity of the BRCA2 gene on human cells remains unclear. (ijbs.com)
In support of this hypothesis, heterozygosity for a BRCA2 mutation has been shown to cause sensitivity to DNA damage agents and reduced RAD51 focus formation after irradiation in the chicken B cell line DT40 [ 16 ]. (ijbs.com)
Additionally, chromosomal rearrangements, increased rates of sister chromatid exchanges and double strand breaks have been observed in cells from heterozygous mutation carriers of BRCA2 [ 17 , 18 ]. (ijbs.com)
In this report, we have utilized HT-29 colon cancer cells and have mimicked the heterozygous state of BRCA2 in these cells through RNA interference. (ijbs.com)
The characterization of the resulting cells with regard to key cellular BRCA2 functions is presented here. (ijbs.com)

Inherited mutations in a small number of genes account for about five to ten percent of women's cancers.These inherited variations, identified in breast, ovarian, and endometrial cancer susceptibility, can be characterized in the general population by their frequency and the magnitude of their impact upon a patient (Table 1 ).Some inherited variants occur rarely in the general population, but confer large risks to the individual. (hindawi.com)
Despite these advances made in identifying inherited breast cancer susceptibility genes, the vast majority of breast cancers are sporadic, that is, no identifiable mutation in one of the known breast cancer susceptibility genes. (hindawi.com)
While this may reflect the fact that we have yet to identify the next BRCA gene, it may also reflect the polygenic nature of breast cancer susceptibility. (hindawi.com)
CHEK2 is not only a breast cancer susceptibility gene but also a multi-organ cancer susceptibility gene [15]. (termedia.pl)
8- 10 In attempts to identify new breast and ovarian cancer susceptibility genes, much research has focused on BRCA1 associated proteins. (bmj.com)
Disease susceptibility is associated with variations affecting the gene represented in this entry. (helixlabs.ai)
Carcinogenesis is a multi-step process wherein abrogation of multiple cancer susceptibility genes leads to cancer development. (amegroups.org)

The ATR kinase communicates DNA damage to the cell and activates DNA damage checkpoints, which arrest the cell cycle to provide time for repairs. (yale.edu)
The protein encoded by this gene belongs the PI3/PI4-kinase family, and is most closely related to ATM, a protein kinase encoded by the gene mutated in ataxia telangiectasia. (utsouthwestern.edu)
This kinase has been shown to phosphorylate checkpoint kinase CHK1, checkpoint proteins RAD17, and RAD9, as well as tumor suppressor protein BRCA1. (utsouthwestern.edu)
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)
The presence of replication stress activates the DNA damage response and downstream checkpoint proteins including ataxia telangiectasia and Rad3 related kinase (ATR), checkpoint kinase 1 (CHK1), and WEE1-like protein kinase (WEE1), which trigger cell cycle arrest while protecting and restoring stalled replication forks. (bmj.com)
In addition, we investigated several cell cycle-related proteins and found that co-knockdown of hTopBP1 and hMYH significantly diminished cell cycle arrest due to compromised checkpoint kinase 1 (Chk1) activation. (biomedcentral.com)
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)
Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor. (abcam.cn)
and Other Mitotic Proteins Are Decreased in DNA-Dependent Protein Kinase Catalytic Subunit-Deficient Cells and Rescued by Inhibition of the Anaphase-Promoting Complex/Cyclosome with proTAME but Not Apcin. (xenbase.org)
The zinc finger domain of Tzfp binds to the tbs motif located at the upstream flanking region of the Aie1 (aurora-C) kinase gene. (lookformedical.com)
Ectopic kinase overexpression in any culture cell line leads to polyploidy and centrosome amplification. (lookformedical.com)
Those transformed cells form tumours when implanted in immunodeficient mice, indicating that the kinase is an oncogene. (lookformedical.com)

An example of this class of genes is a mutation in the CHEK2 gene in breast cancer. (hindawi.com)
A mutation, or (increased or abnormal) methylation, in a tumour suppressor gene may adversely affect the expression or transcription of the gene so that the amino acid sequence and hence the primary structure of its polypeptide product is altered. (biotopics.co.uk)
If a mutation occurs in the proto-oncogene, producing an oncogene , more of these proteins are produced and this leads to unregulated cell division, a slower rate of cell differentiation and increased inhibition of the normal cell death, so cells build up, causing cancer and forming a tumour. (biotopics.co.uk)
Unrepaired DNA lesions can lead to cell death, gene mutation and cancer. (biomedcentral.com)
Deletion or mutation of genes coding for Ku70 or Ku80 proteins results in a highly radiosensitive phenotype [10]. (termedia.pl)
Sequence analysis of these genes is being used to identify BRCA1/2 mutation carriers, though these efforts are hampered by the high frequency of variants of unknown clinical significance (VUSs). (jci.org)
Individuals carrying a mutation in the breast cancer 1, early onset gene ( BRCA1 ) are at increased risk of breast or ovarian cancer and thus are candidates for risk reduction strategies such as oophorectomy and mastectomy. (jci.org)
Genomic instability caused by mutation of the checkpoint molecule TP53 may endow cancer cells with the ability to undergo genomic evolution to survive stress and treatment. (biomedcentral.com)
We attempted to gain insight into the potential contribution of ovarian cancer genomic instability resulted from TP53 mutation to the aberrant expression of multidrug resistance gene MDR1 . (biomedcentral.com)

We have explored the regulation of signalling pathways by p63 and BRCA1 that are involved in growth control, differentiation and stem cell regulation. (biomedcentral.com)
We will identify potential regulators of these pathways using microarray analysis to elucidate p63 and BRCA1 co-regulated targets. (biomedcentral.com)
Specifically, we found that LDHC expressing breast cancer cells display an enrichment of genes involved in canonical pathways regulating cell cycle checkpoint control, BRCA1-mediated DNA damage response and NF-kb signaling in response to infection, which is in line with some of our unpublished work. (bmj.com)
Initiation and propagation of tumors reflect underlying genomic alterations such as mutations, polymorphisms, and copy number variations found in genes of multiple cellular pathways. (hindawi.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)
Here we discuss the ATAD5-luciferase assay and expand upon the value of HTS in identifying other potential cancer drugs, focusing on cell-based assays that involve DNA damage or repair pathways. (oncotarget.com)
In the last several years, heterozygosity leading to haploinsufficiency for proteins involved in DNA repair pathways was shown to play a role in genomic instability and carcinogenesis after DNA damage is induced. (aacrjournals.org)
Because the effect of haploinsufficiency for one protein is relatively small, we hypothesize that predisposition to cancer could be a result of the additive effect of heterozygosity for two or more genes, critical for pathways that control DNA damage signaling, repair or apoptosis. (aacrjournals.org)
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)
Nevertheless, a number of alternative repair pathways have been described as protectors of genome stability, especially in HR-deficient cells. (encyclopedia.pub)
Given the cytotoxic nature of these lesions, the cell has developed multiple pathways of DSB repair, some which result in mutagenic repair, and others that use a template to ensure error-free repair. (encyclopedia.pub)
Maintaining genomic integrity is of utmost importance to eukaryotic cells, which have evolved sophisticated mechanisms to ensure speed, accuracy, and an adequate pool of nucleotide and replication factors as well as high-fidelity repair pathways to correct errors occurring during DNA replication. (bmj.com)
The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. (helixlabs.ai)
The mechanisms of radioresistance are still poorly understood, despite it has been suggested that miRNAs play an important role in cell signaling pathways. (frontiersin.org)
Indeed, it has been shown that miRNAs play an important role in gene expression, mainly when associated with the monitoring of several cell and metabolic pathways, being also an essential component of the gene silencing machinery in most eukaryotic organisms ( 4 , 8 ). (frontiersin.org)

This protein and ATM share similarity with Schizosaccharomyces pombe rad3, a cell cycle checkpoint gene required for cell cycle arrest and DNA damage repair in response to DNA damage. (utsouthwestern.edu)
The Fanconi Anemia (FA) core complex localizes to chromatin during the S phase and in response to DNA damage. (kupferlab.org)
Colocalisation of BARD1 with BRCA1 and RAD51 in response to DNA damage indicates a role in DNA repair, 19, 20 which is supported by the recent observation of BARD1 participation along with BRCA1 in homology directed repair of chromosome breaks. (bmj.com)
In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. (affbiotech.com)
To address this issue, primary mouse cells, haploinsufficient for one or two proteins, ATM and RAD9, related to the cellular response to DNA damage were examined. (aacrjournals.org)
The cellular response to DNA damage involves an intricate network of enzymes responsible for sensing, signaling, and repairing damaged DNA, as well as the regulation of cell cycle checkpoints that collectively maintain genomic integrity 2 . (nature.com)
During ATR signaling in response to DNA damage, Rad17 forms a complex with 9-1-1 and loads onto stalled replication forks [ 4 - 9 ]. (biomedcentral.com)
Involved in transcriptional regulation of P21 in response to DNA damage. (helixlabs.ai)
Furthermore, DNA-PKcs is required to prevent mitotic catastrophe in response to DNA damage ( 13 ). (amegroups.org)

For example, King has identified that if BRCA1 tumors stop expressing the 53BP1 or REV7 protein-both of which play a role in repairing DNA double-strand breaks-they become resistant to PARP inhibitors. (yale.edu)
FA patients are especially prone to head and neck tumors as adults, and non-FA patients' tumors have a high percentage of FA gene somatic mutations. (kupferlab.org)
Comprehensive genomic tumor profiling helps to detect clinically relevant mutations in cancer-associated genes of solid tumors and provides valuable information for selecting the most efficient treatment for each patient. (cegat.com)
In later studies, RAD52 deficiency has been shown to be synthetically lethal with defects in BRCA genes, making RAD52 an attractive therapeutic target, particularly in the context of BRCA-deficient tumors. (encyclopedia.pub)
Small tumors have a greater percentage of actively dividing cells than do large tumors. (msdmanuals.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)

Mutations in other tumor suppressor genes like TP53, PTEN, CDH1, ATM, CHEK2 and PALB2, and oncogenes like KRAS, BRAF and ERBB2 have also been linked with an increased risk of HBOC. (wikipedia.org)
The genes TP53 and CHEK2 are also associated with an increased risk of breast cancer. (biotopics.co.uk)

Furthermore, causal network analysis revealed a higher-level regulation by miR378a-3p (p=1.4e-7, z=-3.117), affecting the mechanistic networks and ultimately promoting tumor cell viability and proliferation, tumor cell movement and cell cycle progression in LDHC expressing cells. (bmj.com)
Eukaryotic cells have developed exquisite mechanisms that monitor and coordinate cell cycle progression with repair of DNA damage to maintain genome integrity. (biomedcentral.com)
A major conclusion from these data is that, contrary to one of the current views on tumorigenesis, inactivation of one allele of a tumor suppressor gene is enough to contribute to tumor progression. (aacrjournals.org)
Variations in these genes are known to significantly impact tumor pathogenesis, progression, and metastasis. (cegat.com)
In the presence of errors or damage during DNA replication, cell cycle checkpoint nodes and repair machinery work in concert to retard cell cycle progression until sufficient repair has been achieved. (bmj.com)
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)
Required for normal cell cycle progression from G2 to mitosis. (helixlabs.ai)
For instance, DNA replication and DNA damage checkpoints delay cell cycle progression until each chromosome is fully replicated and physically intact. (rupress.org)

This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. (cancerindex.org)
TP53 is a checkpoint molecule that maintains genomic stability, prevents cell mitosis and induces apoptosis following abnormal chromosome segregation or chemical damage to DNA sequences [ 9 , 10 ]. (biomedcentral.com)
TAR syndrome is genetically defined by the combination of a microdeletion on chromosome 1 which includes the gene RBM8A, and a single nucleotide polymorphism (SNP) in the second RBM8A allele. (bvsalud.org)
Practically, cycle regulation, chromosome stability and epigenetic F9 cells allow for the efficient metabolic labelling of the modification, in both mouse and human oocytes SILAC reference in vitro, overcoming the difficulty of directly labelling oocytes in vivo. (gotomydoctor.com)
The mouse Tzfp gene, mapped to chromosome 7 B2-B3, encodes a 465-amino acid transcription factor containing a conserved N-terminal BTB/POZ domain and three C-terminal PLZF-like C(2)H(2) zinc fingers. (lookformedical.com)
Each chromosome harbors essential genes. (rupress.org)
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)
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)

Mutations in BRCA1 are thought to be responsible for more than 80% of inherited breast-ovarian cancer. (helixlabs.ai)

3) How does the cell protect genome stability in response to DNA replication stress? (mdanderson.org)
This protective effect of preaccumulated p53 was mediated, at least in part, by the increased expression of CDKN1A/p21, subsequent down-regulation of BRCA1, and impaired JNK activation accompanied by decreased association of replication protein A with chromatin. (rupress.org)
Replication stress is the most common source of endogenous damage and is usually repaired by HR proteins [ 7 ] [ 8 ] . (encyclopedia.pub)
It was also recently shown that PARP-1 is a sensor of unligated Okazaki fragments during DNA replication 16 and cells deficient in ribonucleotide excision repair are sensitized to PARP inhibition 17 . (nature.com)
Any obstacles encountered by cells in this process can lead to 'replicative stress' ( Figure 1 ), 1 which may be overcome by replicative stress response proteins, but deficiencies in this response result in accumulated errors in DNA replication and loss of genomic integrity, which lead to cell death. (bmj.com)
Human DNA topoisomerase II-binding protein 1 (hTopBP1) plays an important role in DNA replication and the DNA damage checkpoint pathway. (biomedcentral.com)
Human DNA topoisomerase II-binding protein 1 (TopBP1) and its orthologs play important roles in DNA replication and checkpoint control [ 1 ]. (biomedcentral.com)
checkpoint adaptor and DNA replication factor. (xenbase.org)

However, alterations to tumour suppressor genes can lead to the development of tumours. (biotopics.co.uk)
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)
A recurring problem in the clinic is that many detectable changes within the BRCA1 gene produce subtle alterations to the protein that are not easily recognized as either harmful (loss-of-function) alleles or harmless and thus inconsequential polymorphisms. (jci.org)
Subsequent improved understanding of the molecular alterations present in the cancer cell has enabled the development of targeted therapies for some forms of cancer. (nature.com)

This gene is involved in the repair of DNA double-strand breaks by homologous recombination and it functionally complements Chinese hamster irs1, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents. (cancerindex.org)
Importantly, we discovered that ES cells rescued by S1497A BRCA1 exhibited significant hypersensitivity after γ-irradiation. (jci.org)

It effectively stimulates mitosis and extra cell division. (biotopics.co.uk)
Contrary to cells treated with a siRNA, cells treated with siRNAs against Bora often displayed multipolar spindles in mitosis, a phenotype that is also seen upon TPX2 RNAi Geneticin distributor and after injection of antibodies blocking Aurora A function. (others-signal.com)
The G 2 gap phase further separates S-phase from mitosis, allowing for continued cell growth and maturation before cell division. (rupress.org)

The S. cerevisiae checkpoint protein Rad17, the orthologue of human Rad1, forms a homocomplex in response to treatment with DNA damaging agents, and the complex is required for yeast survival after exposure to genotoxic agents [ 12 ]. (biomedcentral.com)

BRCA1 was identified in 1994 as one of the genes predisposing to early-onset breast and ovarian cancer. (biomedcentral.com)

In support, downstream effector analysis demonstrate that LDHC silencing negatively affects biological functions such as cellular development, cellular growth and proliferation, cell migration and cell infiltration. (bmj.com)
Cells are constantly exposed to stresses from cellular metabolites as well as environmental genotoxins. (biomedcentral.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)
The generation of cellular models of drug resistance has been pivotal in unravelling the main effectors of resistance to traditional chemotherapy at the molecular level (i.e. intracellular drug inactivation, detoxifying systems, defects in DNA repair, apoptosis evasion, membrane transporters and cell adhesion). (nature.com)
UV irradiation represents a major challenge to genomic integrity throughout the evolution of terrestrial organisms, resulting in the development of specific mechanisms that govern the cellular response to UV-induced DNA damage. (rupress.org)
E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. (helixlabs.ai)
Reproduction (2014) 148 55-72 (Thus, ageing of oocytes may The 'maternal age effect' in reproduction, characterized be viewed as a life-long maintenance of cellular by a negative relationship between maternal age and homeostasis in the same cell, unlike ageing of the male reproductive success, is a poorly understood phenom- germline. (gotomydoctor.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)
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)

25 BARD1 also regulates the subcellular localisation of BRCA1, both by translocating BRCA1 into the nucleus and by inhibiting its nuclear export. (bmj.com)
Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. (helixlabs.ai)

In this study we developed a functional assay using mouse ES cells to study variants of BRCA1. (jci.org)
We introduced BAC clones with human wild-type BRCA1 or variants into Brca1-null ES cells and confirmed that only wild-type and a known neutral variant rescued cell lethality. (jci.org)
Furthermore, we used this assay to determine the effects of BRCA1 variants on cell cycle regulation, differentiation, and genomic stability. (jci.org)
Our results demonstrate that this ES cell-based assay is a powerful and reliable method for analyzing the functional impact of BRCA1 variants, which we believe could be used to determine which patients may require preventative treatments. (jci.org)
This strategy should provide new avenues for clinicians to interpret results of genetic testing of BRCA1 variants and for researchers to study the basic molecular mechanisms of BRCA1 function in in vivo model systems. (jci.org)
Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD) is a relatively common inborn error of metabolism, but due to difficulty in accurately predicting affected status through newborn screening, molecular confirmation of the causative variants by sequencing of the ACADVL gene is necessary. (bvsalud.org)

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)
21 Furthermore, interaction between the BARD1/BRCA1 heterodimer and cleavage stimulation factor subunit 1 (CSTF1, also called CstF-50) represses the polyadenylation machinery, presumably to prevent inappropriate mRNA processing at sites of DNA repair. (bmj.com)

Although the exact function of BRCA1 remains to be defined, roles in DNA damage repair, cell cycle checkpoint control, transcriptional regulation and, more recently, ubiquitination have been inferred. (biomedcentral.com)
BARD1, unlike BRCA1, also contains a centrally located sequence of three ankyrin repeats 11 that are found in many proteins involved in transcriptional regulation. (bmj.com)

Those mechanisms affect which kind of therapies might work once cancer patients relapse on PARP inhibitors, a treatment that stops PARP proteins from repairing DNA damage in cancer cells and leads to cell death. (yale.edu)
She is working to design a clinical trial for ATR inhibitors in BRCA1 patients with fellow Gray Foundation team member Patricia LoRusso, DO , professor of medicine and associate cancer center director of experimental therapeutics. (yale.edu)
It has been reported that Ku-DNA binding inhibitors modulate the DNA damage response in response to DNA DSB [11]. (termedia.pl)
These inhibitors inhibit NHEJ-catalyzed DSB repair and sensitize in vitro cancer cells to DSB-inducing agents. (termedia.pl)
Small molecule inhibitors designed to target the DNA damage sensors, such as inhibitors of ataxia telangiectasia-mutated (ATM), ATR, CHK1 and WEE1, impair smooth cell cycle modulation and disrupt efficient DNA repair, or a combination of the above, have demonstrated interesting monotherapy and combinatorial activity, including the potential to reverse drug resistance and have entered developmental pipelines. (bmj.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)
The clinical success of immune checkpoint inhibitors has dramatically changed outcomes for patients across cancer types. (biomedcentral.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)

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)

As main findings, 23 miRNAs were already identified as being involved in genetic regulation of PCa cell response to RT. (frontiersin.org)
Taken together, our results indicate that Tzfp recognizes a sequence-specific motif (tbs) and may play a role in the regulation of the genes carrying the tbs. (lookformedical.com)

Genome wide association studies, fluorescence in situ hybridization, comparative genomic hybridization, and candidate gene studies have enumerated genetic contributors to cancers in women. (hindawi.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)

Breast cancer refers to the uncontrolled division of breast cells. (wikipedia.org)
Symptoms are more likely to emerge after metastasis, a process where cancer cells spread from the site of origin to different organs through blood and lymphatic vessels and form a new tumor. (wikipedia.org)
Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings. (cancerindex.org)
Knockdown of BRCA1 and p63 leads to enhanced proliferation of breast cancer cell lines and increased stem cell numbers as assayed for by mammosphere culture and Aldefluor assay. (biomedcentral.com)
Background Cancer testis antigens (CTAs) have gained interest in the field of anti-cancer therapy as they offer the opportunity to target tumor cells with little off/on-target side effects given their restricted expression patterns. (bmj.com)
Several CTAs have been implicated as mediators of cancer hallmarks including cancer metabolism, proliferation, survival, and cell motility. (bmj.com)
Lactate dehydrogenase C (LDHC) expression has been observed in various cancer types and likely confers a survival advantage to tumor cells through metabolic reprograming. (bmj.com)
This study aimed to explore the changes in the transcriptome of breast cancer cells upon in vitro LDHC targeting. (bmj.com)
Methods We silenced LDHC expression in two breast cancer cell lines (BT549, HCC1954) and investigated the downstream effects on the tumor cell transcriptome. (bmj.com)
In addition, differentially expressed genes were subjected to regulatory network analyses and expression of key regulators was interrogated in the TCGA breast cancer dataset. (bmj.com)
In the three years since, Yale's team has made significant advances in targeting the BRCA gene-dependent DNA repair axis for cancer therapy. (yale.edu)
Consideration of tumor heterogeneity is therefore important in the critical analysis of gene associations in cancer. (hindawi.com)
Cancer cells can recur if they are not completely removed. (biotopics.co.uk)
This reverses its normal inhibitory action, resulting in the rapid and uncontrollable cell division which is the hallmark of cancer. (biotopics.co.uk)
Tumour suppression is achieved via the inhibition of cell division, induction of apoptosis (cell death) to remove altered cells, DNA damage repair, and inhibition of mechanisms that cause spread of cancer cells to other parts of the body (metastasis). (biotopics.co.uk)
Defects in the ability of cells to properly respond to and repair DNA damage result in genomic instability and underlie many forms of cancer. (mdanderson.org)
Recent advances in understanding of the mechanisms involved in DNA damage signaling and repair have opened up a new avenue in treatment of breast cancer, i.e. (termedia.pl)
DNA repair targeted therapy, which kills cancer cells preventing DNA repair [1-3]. (termedia.pl)
A spectacular example of this approach to treatment of breast cancer is application of a poly (ADP-ribose) polymerase (PARP) inhibitor, such as olaparib, to patients with germline BRCA1 mutations [4, 5]. (termedia.pl)
11- 13 The finding of breast cancer associated mutations within the RING finger domain of BRCA1 , disrupting BRCA1/BARD1 interaction, 11, 14 and the occurrence of BARD1 missense mutations in breast cancer patients, 15- 17 implies participation of BARD1 in BRCA1 mediated tumour suppression. (bmj.com)
One example of such an assay is the ATAD5-luciferase HTS assay, which identified three antioxidants that could kill cancer cells without inducing mutagenesis. (oncotarget.com)
Loss of function of oncogenes, tumor suppressor genes and DNA damage processing genes has been implicated in the development of many types of cancer, but for the vast majority of cases, there is no link to specific germ line mutations. (aacrjournals.org)
Women who are heterozygous carriers of mutations in either gene have a 60%-80% lifetime risk of breast cancer and a 10%-40% lifetime risk of ovarian cancer ( 1 ), reflecting a very high penetrance. (jci.org)
Ovarian cancer cell DNA ploidy was determined using Feulgen-stained smears or flow cytometry. (biomedcentral.com)
In addition, the novel cancer stem cell paradigm raises the prospect of cell-targeted therapies instead of treatment directed against the whole tumour. (nature.com)
DSBs are cytotoxic lesions, which if left unrepaired could lead to genomic instability, cancer and even cell death. (springeropen.com)
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)
If left unrepaired, DSBs can cause chromosomal aberrations, mutagenesis, and cell death, leading to the development of severe diseases including cancer [ 1 ] [ 2 ] . (encyclopedia.pub)
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)
One of the treatments applied in cancer is radiotherapy (RT), a therapeutic modality that uses ionizing radiation to induce damage in unwanted cells. (frontiersin.org)
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)
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)
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 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)
Many factors are involved in causing and permitting the unregulated proliferation of cells that occurs in cancer. (msdmanuals.com)
Overview of Cancer Cancer is an unregulated proliferation of cells. (msdmanuals.com)
Cancer cells, particularly those arising from the bone marrow or lymphatic system, may have a short generation time, and there usually are a smaller percentage of cells in G0 (resting phase). (msdmanuals.com)
A subpopulation of cells within a cancer has the properties of stem cells. (msdmanuals.com)
A cancer may release cells into the circulation at a very early stage of development. (msdmanuals.com)
Circulating cancer cells are present in many patients with advanced cancer and even in some with localized disease. (msdmanuals.com)
Although most circulating cancer cells die, an occasional cell may penetrate into tissues, generating a metastasis at a distant site. (msdmanuals.com)
Experiments suggest that the abilities to invade, migrate, and successfully implant and stimulate new blood vessel growth are all important properties of the cells that cause metastases, which are likely a subpopulation of the primary cancer. (msdmanuals.com)
Cancer cells often present neoantigens on their cell surface that can be detected as "non-self" by the immune system, resulting in an attack by the immune system. (msdmanuals.com)

Activation of ATR phosphorylates a number of downstream proteins that coordinate the cell cycle checkpoint. (biomedcentral.com)

No difference in RAD51 subcellular localization and focus formation was observed between control and mimicked heterozygous cell lines. (ijbs.com)

Thirty SNPs of well-defined functional genes were investigated. (cancerindex.org)
p63 was identified as a positively regulated BRCA1 target gene through microarray analysis, and the functional significance of the BRCA1/p63 signalling axis was investigated. (biomedcentral.com)
In fact they they often code for proteins that stimulate cell division, prevent cell differentiation or regulate programmed cell death (apoptosis) within normal tissues and in this way they cause a controlled turnover of functional cells within an organ. (biotopics.co.uk)
The phenotype of Bard1 null mice was found to be remarkably similar to that of Brca1 nulls, further emphasising the functional relationship between these two proteins. (bmj.com)

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)
The ataxia telangiectasia and Rad3-related protein (ATR) signaling cascade is an important pathway involved in the checkpoint control mechanism [ 3 ]. (biomedcentral.com)
Thus, hTopBP1 constitutes an important part of the ATR signaling pathway and acts as a molecular bridge that associates the independently recruited 9-1-1 and ATR-ATRIP complexes, thereby leading to checkpoint activation [ 4 ]. (biomedcentral.com)
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)
promotes DNA damage response pathway from a single-strand break. (xenbase.org)
DNA-PKcs and the NHEJ pathway are also essential for V(D)J recombination during T and B cell lymphocyte development. (amegroups.org)

hTopBP1 and hMYH were involved in ATR-mediated Chk1 activation, moreover, both of them were associated with ATR and hRad9 which known as checkpoint-involved proteins. (biomedcentral.com)
The accumulation of hTopBP1 on chromatin and its subsequent interaction with hRad9 lead to cell cycle arrest, a process mediated by Chk1 phosphorylation and ataxia telangiectasia and Rad3-related protein (ATR) activation. (biomedcentral.com)
Our results suggested that hMYH is necessary for the accumulation of hTopBP1 to DNA damage lesion to induce the association of hTopBP1 with 9-1-1 and that the interaction between hMYH and hTopBP1 is essential for Chk1 activation. (biomedcentral.com)

The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. (affbiotech.com)
is a direct negative regulator of the DNA-damage response. (xenbase.org)

Search the gene expression profiles from curated DataSets in the Gene Expression Omnibus (GEO) repository. (cancerindex.org)
Expression of BRCA1 or p63 in a background of low BRCA1 and p63 results in decreased cell proliferation. (biomedcentral.com)
Knockdown of BRCA1 and p63 leads to the loss of S100A2 expression. (biomedcentral.com)
In a p63 and BRCA1 null background, expression of S100A2 results in a reduction of cell proliferation. (biomedcentral.com)
The activated version of this acts as a transcription factor regulating various gene expression events involved in the development of breast tissue in puberty and pregnancy. (biotopics.co.uk)
It is likely that increased Rad9 expression is needed for proliferation of tumor cells by mechanisms such as getting beyond (tolerating) oncogene-induced replicative stress and enhancing DNA repair capability. (biomedcentral.com)
How Reliable Are Gene Expression-Based and Immunohistochemical Biomarkers Assessed on a Core-Needle Biopsy? (lu.se)

2) How does chromatin modification at sites of DNA damage regulate DNA repair and transcription? (mdanderson.org)
26 The suggested role in TP53 dependent apoptotic signalling 27 and interaction with the ankyrin repeats of proto-oncoprotein BCL3, thereby possibly modulating the activity of transcription factor NFKB, 28 represent BRCA1 independent functions of BARD1. (bmj.com)
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)
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)
A mainstream hypothesis is that maternal ageing of oocytes has its roots in gene transcription. (gotomydoctor.com)
factor(s) relies on gene transcription that oocytes largely Oocytes spend most of their time quiescent in primordial perform during follicular growth prior to ovulation, and follicles, mature over days or weeks during follicular the transcriptional activities of oocytes may be influ- growth and then become quiescent again near the enced by maternal age. (gotomydoctor.com)

1) How does the hereditary breast tumor suppressor BRCA1 interaction network suppress breast tumor development? (mdanderson.org)
To determine whether Rad1 functions to maintain genomic stability and prevent tumor development, we generated Mrad1 mutant mice by gene targeting. (biomedcentral.com)
Another conclusion from most of the cases is that animals or cells haploinsufficient for the specified proteins have higher transformation rates after DNA damage is induced, but when their DNA is not significantly damaged by exogenous sources, tumor development rates are the same as for their wild-type counterparts. (aacrjournals.org)
These are extremely hazardous for a cell, because if left unrepaired, DSBs can have pathological consequences, such as cell death, or drive cells to genomic instability and tumor development. (nature.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)

Keratinocytes isolated from Mrad1 +/- mice had significantly more spontaneous DNA double strand breaks, proliferated slower and had slightly enhanced spontaneous apoptosis than Mrad1 +/+ control cells. (biomedcentral.com)
The effects of heterozygous deletion of Mrad1 on proliferation and apoptosis of keratinocytes is different from those resulted from Mrad9 heterozygous deletion (from our previous study), suggesting that Mrad1 also functions independent of Mrad9 besides its role in the Mrad9-Mrad1-Mhus1 complex in mouse cells. (biomedcentral.com)
It is also involved in cell cycle arrest and apoptosis [17]. (termedia.pl)
The pathogenetic mechanisms of IBMFSs remain to be characterized fully, but an overarching hypothesis states that different stresses elicit TP53-dependent growth arrest and apoptosis of hematopoietic stem, progenitor, and precursor cells. (bvsalud.org)

So when a $1 million grant became available for BRCA gene research from the Gray Foundation in 2018, a diverse team of Yale experts whose perspectives on BRCA gene-driven malignancies provide a 360-degree view from bench to bedside combined their collective skills to secure the sizable gift . (yale.edu)

As in FA, codanin, the protein whose gene is mutated in CDA has no known function, and additional genes accounting for additional genetic complementation groups remain to be cloned and identified. (kupferlab.org)
Failure to repair DSBs can lead to unwanted consequences, such as loss of genetic information, chromosomal rearrangements and even cell death. (springeropen.com)

In this issue of the JCI , Chang, Sharan, and colleagues describe a novel system to evaluate human BRCA1 alleles for in vivo function using BACs containing human BRCA1 vectors in mouse cells and embryos (see the related article beginning on page 3160). (jci.org)
According to Knudson's two hit hypothesis for tumor suppressor genes [ 15 ], loss of both alleles must occur prior to tumor growth. (ijbs.com)

These cells can be activated ex vivo to exhibit a potent antitumor effector function. (biomedcentral.com)

Her laboratory takes multidisciplinary approach to identify important players in the DNA damage response and define the roles of these genes in maintaining genomic stability and tumor suppression. (mdanderson.org)
Rad1 plays crucial roles in DNA repair and cell cycle checkpoint control, but its contribution to carcinogenesis is unknown. (biomedcentral.com)
Within the core complex, both FANCA and FANCG are phosphorylated (P). In the presence of an intact core complex, FANCD2 is monoubiquitinated (Ub) on K561 and colocalizes in nuclear foci with BRCA1, where it carries out its roles in DNA repair and/or cell cycle control. (kupferlab.org)

Interestingly, the miR378a causal network also indicated inhibition of the immune response in LDHC positive cells. (bmj.com)
Here we show that in Saccharomyces cerevisiae a single DSB causes transcriptional inhibition of proximal genes independently of Tel1/ATM and Mec1/ATR. (elifesciences.org)

The maintenance of genome integrity is critical for cell survival. (encyclopedia.pub)

One of the oxidative DNA lesions frequently generated upon exposure of cells to reactive oxygen species (ROS) is 7,8-dihydro-8-oxoguanine (8-oxoG) [ 13 ]. (biomedcentral.com)
How do cells sense DNA lesions? (xenbase.org)

Unlike the male germline, the bulk of The synthesis of the aforementioned molecular oocytes do not have a gonial stem cell population. (gotomydoctor.com)

Methods include sequence analysis and gene-targeted deletion/duplication analysis. (wikipedia.org)
The majority of DSBs in a cell are repaired by non-homologous end-joining (NHEJ), which ligates blunt ends in a sequence-independent manner and can result in small insertions or deletions (indels) [ 1 ] . (encyclopedia.pub)
These single-stranded DNA 'tails' are then free to interact with an intact copy of the same DNA sequence from elsewhere in the cell's nucleus, which is used as a guide when repairing the damage. (elifesciences.org)
In this report, we describe a testis zinc finger protein (Tzfp) that binds to the upstream flanking sequence of the Aie1 gene. (lookformedical.com)
The zinc finger domain of Tzfp binds to the TGTACAGTGT motif (Tzfp binding site, termed tbs) located at the upstream flanking sequence of the Aie1 gene by gel mobility shift, DNase I footprinting, and competition analyses. (lookformedical.com)

Two SNPs in X-Ray Repair Cross Complementing 2 gene (XRCC2) rs2040639 and interferon gamma (IFNG) rs2069705 genes were found to be associated with ARSR. (cancerindex.org)
Of even greater excitement is Bindra's comprehensive library of DNA repair inhibitor and damaging agents. (yale.edu)
DNA damage caused by these genotoxins can be efficiently fixed by DNA repair in cooperation with cell cycle checkpoints. (biomedcentral.com)
It is believed that this complex is important for the function of these three proteins in DNA repair as well as activation of cell cycle checkpoints. (biomedcentral.com)
It is a tumor suppressor gene, involved in DNA DSB repair through the process of homologous recombination [16]. (termedia.pl)
The results show that cells having low levels of both ATM and RAD9 proteins are more sensitive to transformation by radiation, have different DNA double-strand break repair dynamics and are less apoptotic when compared with wild-type controls or those cells haploinsufficient for only one of these proteins. (aacrjournals.org)
Our conclusions are that under stress conditions, the efficiency and capacity for DNA repair mediated by the ATM/RAD9 cell signaling network depend on the abundance of both proteins and that, in general, DNA repair network efficiencies are genotype-dependent and can vary within a specific range. (aacrjournals.org)
Many anticancer drugs, such as platinum compounds, alkylating agents and nitrosoureas, cause direct damage to the structural integrity of the DNA, and resistance to these compounds results from activation of DNA repair systems. (nature.com)
Recombination based mechanisms are crucial for both the repair and tolerance of DNA damage that vexes both strands of the double helix [ 9 ]. (springeropen.com)
Homologous recombination' is one of the main mechanisms used by cells to repair DNA double-strand breaks. (elifesciences.org)

Nat Cell Biol 24(7):1154-1164, 2022. (mdanderson.org)
J Cell Biol (2008) 182 (1): 197-213. (rupress.org)
Cell Chem Biol. (xenbase.org)
Mol Cell Biol. (xenbase.org)
J Cell Biol (2005) 169 (6): 841-846. (rupress.org)

In this study, we show that Tip60 is required for the early DNA damage response (DDR) to UV, including the phosphorylation of histone 2AX, c-Jun N-terminal kinases (JNKs), and ataxia telangiectasia-related substrates. (rupress.org)
The ataxia telangiectasia Rad3-related (ATR) protein responds to UV damage, whereas the ataxia telangiectasia mutated (ATM) protein responds to double-strand breaks (DSBs) caused by ionizing radiation and radiomimetic compounds. (medscape.com)

Rather, p53 accumulation by either knockdown of Mdm2 or addition of an Mdm2 inhibitor, Nutlin-3, before irradiation strongly attenuated the UV-induced DDR and increased cell survival. (rupress.org)
Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. (helixlabs.ai)

Conversely, loss of S100A2 in a BRCA1 and p63 expressing background leads to increased proliferation. (biomedcentral.com)
Examples of cell-based assays include RNAi [ 3 ], second messenger, cell proliferation, and reporter assays [ 4 ]. (oncotarget.com)

In introductory biology classrooms, cell and molecular concepts are often taught separate from those related to evolution and ecology, and usually in completely different courses. (biomedcentral.com)

Its prominent properties are A lack of cell differentiation Local invasion of adjoining tissue Metastasis, which is spread to distant sites through. (msdmanuals.com)

Anatomy23

Organisms6

Diseases13

Chemicals and Drugs110

Analytical, Diagnostic and Therapeutic Techniques and Equipment21

Phenomena and Processes92

Disciplines and Occupations1

Information Science3

Named Groups1

Health Care4

BRCA237

Susceptibility7

Kinase12

Mutation9

Pathways15

Response to DNA damage9

Tumors6

CHEK22

Progression8

Chromosome8

Mutations in BRCA11

Replication8

Alterations4

Hypersensitivity2

Mitosis3

RAD171

Early-onset1

Cellular10

Regulates2

Variants6

Heterodimer2

Transcriptional regulation2

Inhibitors8

BRCT1

Regulation2

Cancers2

Cancer44

Downstream1

RAD511

Functional4

Pathway6

CHK13

Regulator2

Expression7

Transcription7

Tumor development4

Instability2

Apoptosis4

BRCA1

Genetic2

Alleles2

Vivo1

Roles3

Inhibition2

Genome integrity1

Lesions2

Germline1

Sequence5

Repair10

Biol5

Ataxia2

Irradiation2

Proliferation2

Molecular1

Differentiation1