Cell response to dna damage damage cell cycle checkpoint gene. Medical search. Frequent questions

Checkpoint kinase 1, commonly referred to as Chk1, is a serine/threonine-specific protein kinase that, in humans, is encoded by the CHEK1 gene. (wikipedia.org)
Two checkpoint kinase subtypes have been identified, Chk1 and Chk2. (wikipedia.org)
In response to DNA damage, a synthetic lethal relationship exists between the cell cycle checkpoint kinase MK2 and the tumor suppressor p53. (nature.com)
The protein encoded by this gene belongs to the Ser/Thr protein kinase family. (caslab.com)
The ATM gene encodes a large protein that belongs to a family of kinases possessing a highly conserved C-terminal kinase domain related to the phosphatidylinositol 3-kinase domain. (bmj.com)
Members of this kinase family have been shown to function in DNA repair and cell cycle checkpoint control following DNA damage. (bmj.com)
8 , 9 The protein is a member of a novel family of large proteins, which show sequence homology to the catalytic domain of phosphatidylinositol 3 kinase, 3 and are implicated in cell cycle regulation, signal transduction, and the response to DNA damage. (bmj.com)
Background: The product of this gene is an essential upstream regulator of checkpoint kinase 1 and triggers a checkpoint arrest of the cell cycle in response to replicative stress or DNA damage. (idhinhibitor.com)
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)
53BP1 is involved in the phosphorylation of various ataxia telangiectasia mutated protein (ATM) substrates such as cell cycle checkpoint kinase 2 (CHEK2) [ 3 , 6 ]. (biomedcentral.com)
In response to DNA double strand breaks, serine at position 15 of the TP53 (p53) tumor suppressor protein is rapidly phosphorylated by the ATM kinase. (reactome.org)
Ku70/80 forms a complex with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to form the full DNA-dependent protein kinase, DNA-PK [7]. (termedia.pl)
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)
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)
ATM is a serine/threonine protein kinase that synchronises rapid DNA damage response (DDR) to DNA double strand breaks (DSBs) with activation of cell cycle checkpoints, DNA repair and apoptosis via p53 activation. (birmingham.ac.uk)

The DNA damage response is a network of signaling pathways that leads to activation of checkpoints, DNA repair and apoptosis to inhibit damaged cells from progressing through the cell cycle. (wikipedia.org)
p53 is a transcription factor that participates in cell cycle checkpoint processes and apoptosis. (lu.se)
Potential synergistic effects of various combinations including these compounds were tested by measuring cancer cell proliferation and apoptosis. (frontiersin.org)
Activated p53 transcriptionally regulates hundreds of genes that are involved in multiple biological processes, including in DNA damage repair, cell cycle arrest, apoptosis and senescence. (nih.gov)
In this Review, we discuss the multiple molecular mechanisms of p53 regulation and how they modulate the induction of apoptosis or cell cycle arrest following DNA damage. (nih.gov)
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)
The p53-inducible gene 3 (PIG3) was originally indentified by Polyak et al in the analysis of p53-induced genes related to the onset of apoptosis ( 1 ). (ijbs.com)
In some p53 mutants, induction of cell cycle arrest, but not apoptosis was found to be associated with a lack of induction of PIG3 expression ( 2 ). (ijbs.com)
Additionally, PIG3 mediates cancer cell death through the GPx3 pathway, and knocking down PIG3 or blocking the interaction between PIG3 and GPx3 would abolish the increase in ROS and apoptosis ( 5 ). (ijbs.com)
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)
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)
Activation of the p53 tumor suppressor upon DNA damage elicits either cell cycle arrest or apoptosis, and the precise mechanism governing cell fate after p53 response has not been well defined. (figshare.com)
Although RPS27L mRNA levels were consistently induced after diverse p53 activating signals, its change in protein level was stimuli-dependent: it was up-regulated when cells were arrested in response to DNA-damaging agents Adriamycin or VP16 but was down-regulated when cells underwent apoptosis in response to antimetabolite agent 5-fluorouracil. (figshare.com)
Depletion of RPS27L resulted in deficiency in DNA damage checkpoints, leading to conversion of DNA damage-induced p53 response from cell cycle arrest to apoptosis. (figshare.com)
Through this mechanism, RPS27L induction by p53 facilitates p21-mediated cell cycle arrest and protects against DNA damage-induced apoptosis. (figshare.com)
It is also involved in cell cycle arrest and apoptosis [17]. (termedia.pl)
Ataxia Telangiectasia Mutated (ATM) protein coordinates responses to DNA double strand breaks (DSBs) and the ATM-null status caused by biallelic ATM gene inactivation in chronic lymphocytic leukemia (CLL) results in resistance to p53-dependent apoptosis. (birmingham.ac.uk)
However, in established cancer cells, such DNA repair system may prevent further DNA damage in their progeny and decrease in apoptosis resulting in enhancement of tumor growth. (biomedcentral.com)
Thus, in addition to its checkpoint control function, hRad9 may play a role in regulating apoptosis. (biomedcentral.com)

Chk1 must inactivate in order for the cell to transition from the G2 phase into mitosis, Chk1 expression levels are mediated by regulatory proteins. (wikipedia.org)
However, activation of Chk1 is not solely dependent on ATR, intermediate proteins involved in DNA replication are often necessary. (wikipedia.org)
The regulation and function of Fanconi anemia (FA) and breast cancer susceptibility (BRCA) genes/proteins is of particular interest, along with identifying FA-BRCA interacting proteins and understanding how FA-BRCA genes/proteins are affected by sequence variants. (cincinnatichildrens.org)
Additional related interests include applying insights into FA-BRCA genes/proteins to improve therapeutic approaches to cancer and related diseases, proton radiation biology, and how to ameliorate CRISPR-Cas9 mediated gene editing by enhancing HR-dependent repair of DSBs generated by Cas9. (cincinnatichildrens.org)
This protein acts to integrate signals from ATM and ATR, two cell cycle proteins involved in DNA damage responses, that also associate with chromatin in meiotic prophase I. Phosphorylation of CDC25A protein phosphatase by this protein is required for cells to delay cell cycle progression in response to double-strand DNA breaks. (caslab.com)
4 , 10 There is evidence to suggest that these proteins respond to DNA damage by phosphorylating one or more substrates, including p53, c-Abl, and replication protein A (RPA), to recruit proteins to regions of DNA repair and/or to activate radiation signal transduction pathways. (bmj.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)
J-H Lee et al also have provided the first evidence showing that PIG3 is closely associated with the induction and maintenance of the phosphorylation of H2AX and some other DDR proteins after DNA damage induced by NCS ( 8 ). (ijbs.com)
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)
Deletion or mutation of genes coding for Ku70 or Ku80 proteins results in a highly radiosensitive phenotype [10]. (termedia.pl)
The Mre11-Rad50-Nbs1 protein complex has emerged as a central player in the human cellular DNA damage response, and recent observations suggest that these proteins are at least partially responsible for the linking of DNA damage detection to DNA repair and cell cycle checkpoint functions. (nebraska.edu)
Defining the functional relationships between proteins is critical for understanding virtually all aspects of cell biology. (thebiogrid.org)
Here, the fusion proteins MLL-AF4 (MA4) and AF4-MLL (A4M) were CRISPR/Cas9-genome edited in the AAVS1 locus of HEK293 cells as a model to study MLL fusion-mediated DNA-DSB formation/repair. (ibecbarcelona.eu)
Our laboratory is interested in understanding the mechanisms by which microRNA and checkpoint proteins stall the cell cycle preventing genomic instability and cancer. (nii.res.in)
Whenever genomic lesions are detected during DNA synthesis, they are coated by the single strand DNA binding protein complex, called Replication Protein A, leading to the activation of canonical checkpoint proteins like ATR, Chk1 and p53. (nii.res.in)
Human genome codes for many other single strand DNA binding proteins and we are testing if novel mechanisms of checkpoint activation exist that do not require Replication Protein A. If such mechanisms exist we would like to understand which factors provide the role of DNA binding, how checkpoint proteins like Chk1 and p53 are activated and how signal transduction pathway stalls the cell cycle and DNA replication. (nii.res.in)

p53, mdm-2, p21, and mib-1 expression were not significantly associated with response to chemotherapy, time to progression, or overall survival in the whole patient population or in the docetaxel group. (lu.se)
or =10%) predicted a better response (P = 0.014 and P = 0.046, respectively) to treatment and a longer time to progression in both univariate and multivariate analyses. (lu.se)
Overall, genes are mainly involved in developmental progression and regulation. (github.io)
Changes in methylation of this gene could impact progression of gametogenesis or embryogenesis. (github.io)
Eukaryotic cells have developed exquisite mechanisms that monitor and coordinate cell cycle progression with repair of DNA damage to maintain genome integrity. (biomedcentral.com)
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)
PIG3 knockdown led to an abnormal DNA damage response, including decreased IR-induced phosphorylation of H2AX, Chk1, Chk2 and Kap-1 as well as a prolonged G2-M arrest and aberrant mitotic progression. (ijbs.com)
This prevents the normal progression from G1 to S phase, thus providing a check on replication of damaged DNA (Banin et al. (reactome.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)
In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. (affbiotech.com)
When mammalian cell experiences DNA damage, it activates checkpoint mechanisms to stall the progression of cell cycle and DNA replication. (nii.res.in)
Emerging evidences suggest that microRNA target genes that regulate DNA replication and cell cycle progression and we aim to determine how microRNA regulate the DNA replication machinery as cell progresses from one phase to the next. (nii.res.in)

Activation of Chk1 results in the initiation of cell cycle checkpoints, cell cycle arrest, DNA repair and cell death to prevent damaged cells from progressing through the cell cycle. (wikipedia.org)
Constitutive expression of Chk1 in fission yeast was shown to induce cell cycle arrest. (wikipedia.org)
Studies on Chk1 deficient chicken lymphoma cells have shown increased levels of genomic instability and failure to arrest during the spindle checkpoint phase in mitosis. (wikipedia.org)
Therefore, compared to normal p53-proficient cells, p53-defective cells are more reliant on MK2 activity, which drives an alternative cell cycle checkpoint pathway that stabilizes the CKI inhibitors p27 Kip1 and Gadd45α in order to maintain G 1 /S and G 2 /M arrest after certain types of DNA damage 16 , 18 . (nature.com)
In response to DNA-damaging agents, the wild-type p53-activated fragment 1 (WAF1 also known as p21) is an important downstream effector in the p53-specific growth arrest pathway. (lu.se)
It is required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. (caslab.com)
RAD9A is highly similar to Schizosaccharomyces pombe rad9, a cell cycle checkpoint protein required for cell cycle arrest and DNA damage repair in response to DNA damage. (avivasysbio.com)
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)
Normally, structural damage of DNA by endogenous and environmental agents is followed by replication checkpoint arrest at the G2/M transition in order to allow for repair before proceeding in the cell cycle. (biomedcentral.com)
Treatment with etoposide consistently induced cell cycle arrest in S/G2/M independent of MA4/A4M expression, revealing a proper activation of the DNA damage checkpoints. (ibecbarcelona.eu)

Because BRCA mutations are observed in fewer than 10% of cancer patients (cBioPortal: 6.7%) 11 , 12 , 13 the identification of additional genes that share synthetic lethal sensitivity relationships with mutated oncogenes or tumor suppressors would greatly enhance the implementation of tumor cell-specific synthetic lethal sensitivity to improve an anticancer therapeutic response. (nature.com)
Because most tumors are deficient in one or more aspects of the function of the p53 tumor suppressor, either as a consequence of mutations within p53, or impairment of upstream and downstream modulators of p53 activity 19 , targeting MK2 has the potential to selectively enhance tumor cell killing without increasing the genotoxic effects of chemotherapy on normal p53-wild type tissues. (nature.com)
Tumour heterogeneity is a phenomenon where each cell that makes up a tumour, contains mutations that differ from that of other cells in the tumour. (scienceopen.com)
Frequent inactivating mutations of the ATM gene have been reported in patients with rare sporadic T cell prolymphocytic leukaemia (T-PLL), B cell chronic lymphocytic leukaemia (B-CLL), and most recently, mantle cell lymphoma (MCL). (bmj.com)
The presence of inactivating mutations, together with the deletion of the normal copy of the ATM gene in some patients with T-PLL, B-CLL, and MCL, establishes somatic inactivation of the ATM gene in the pathogenesis of lymphoid malignancies, and strongly suggests that ATM functions as a tumour suppressor. (bmj.com)
Mutations of the ATR gene have been reported in Seckel patients, who suffer from a rare genetic disease characterized by severe microcephaly and growth retardation. (dundee.ac.uk)
For example, in the hereditary cancer syndromes familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer, mutations have been discovered in the APC gene and DNA mismatch repair genes. (medscape.com)
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)
Mutations of this gene are associated with Seckel syndrome. (utsouthwestern.edu)
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)
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)
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)
The loss of proper response to DNA damage leads to genomic instability such as gene mutations, incomplete replication and the loss or gain of chromosomes to future generations. (biomedcentral.com)
Mutations/deletions in separate genes, each of which alone causes a minimal phenotype, but when combined in the same cell results in a more severe fitness defect or lethality under a given condition. (thebiogrid.org)

This pathway recognizes single strand DNA (ssDNA) which can be a result of UV-induced damage, replication stress and inter-strand cross linking. (wikipedia.org)
These ssDNA structures attract ATR and eventually activates the checkpoint pathway. (wikipedia.org)
Triple treatment showed synergism in terms of exhibiting anti-tumorigenic effects by activating the Hippo YAP signaling pathway in the HCT116 cell line. (frontiersin.org)
Dual RAS/MAPK pathway blockade combining KRAS and MEK inhibitors is more effective than the selective KRAS inhibitor alone in attenuating MAPK activation and unblocking the influx of T cells into the tumor. (bvsalud.org)
Ku70/80 is a heterodimer of two polypeptides, Ku70 (encoded by XRCC6) and Ku80 (encoded by XRCC5), that binds to DNA double-strand break (DSB) ends and is necessary for the non-homologous end joining (NHEJ) pathway of DNA repair [6]. (termedia.pl)
These results identify a novel pathway by which an oncogene influences replication in the absence of DNA damage. (oncotarget.com)
A p53 dependent checkpoint pathway prevents re-replication. (nii.res.in)
The present study provides in vivo evidence that a GSH mediated pathway underlies asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure. (cdc.gov)

Chk1 is a central component of genome surveillance pathways and is a key regulator of the cell cycle and cell survival. (wikipedia.org)
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)
Genotoxic damage causes robust alterations to pathways associated with B cell activation and increased proliferation, suggesting that genotoxic damage initiates not only the normal B cell maturation processes but also mimics activated B cell response to antigenic agents. (biomedcentral.com)
The scsA TOP1 and the scaA NBS1 gene products could functionally interact in pathways that either monitor or repair DNA double-strand breaks. (nebraska.edu)
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)
ATM-null cells are defective in a type of DSB repair that involves homologous recombination and rely on co-operating and compensatory DNA repair pathways for their survival. (birmingham.ac.uk)
Therefore, inhibition of DNA repair pathways to which CLL cells with loss of ATM signalling become addicted could provide 'synthetic lethality' and induce tumour specific killing. (birmingham.ac.uk)
Most of the identified module pairs cover cooperative pathways and components essential to the cell cycle. (biomedcentral.com)

SL originally described a relationship between two genes, where alteration of either gene alone results in viable cells, but alteration (mutation, loss, or inhibition) of both genes simultaneously was lethal. (nature.com)
The association between mutation of the ATM gene and a high incidence of lymphoid malignancy in patients with AT, together with the development of lymphoma in Atm deficient mice, supports the proposal that inactivation of the ATM gene may be of importance in the pathogenesis of sporadic lymphoid malignancy. (bmj.com)
Here, we propose that oncogenic dependency, rather than KRAS mutation per se, plays a dominant role in the immune response to cancer, including late-stage PDAC. (bvsalud.org)
Unrepaired DNA lesions can lead to cell death, gene mutation and cancer. (biomedcentral.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)
An example of this class of genes is a mutation in the CHEK2 gene in breast cancer. (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)

Chk1 coordinates the DNA damage response (DDR) and cell cycle checkpoint response. (wikipedia.org)
Chk1 is required for the initiation of DNA damage checkpoints and has recently been shown to play a role in the normal (unperturbed) cell cycle. (wikipedia.org)
Chk1 impacts various stages of the cell cycle including the S phase, G2/M transition and M phase. (wikipedia.org)
In addition to mediating cell cycle checkpoints, Chk1 also contributes to DNA repair processes, gene transcription, egg production, embryo development, cellular responses to HIV infection and somatic cell viability. (wikipedia.org)
Chk1 monitors DNA replication in unperturbed cell cycles and responds to genotoxic stress if present. (wikipedia.org)
Chk1 recognizes DNA strand instability during replication and can stall DNA replication in order to allow time for DNA repair mechanisms to restore the genome. (wikipedia.org)
Recently, Chk1 has shown to mediate DNA repair mechanisms and does so by activating various repair factors. (wikipedia.org)
Furthermore, Chk1 has been associated with three particular aspects of the S-phase, which includes the regulation of late origin firing, controlling the elongation process and maintenance of DNA replication fork stability. (wikipedia.org)
In response to DNA damage, Chk1 is an important signal transducer for G2/M checkpoint activation. (wikipedia.org)
Activation of Chk1 holds the cell in the G2 phase until ready to enter the mitotic phase. (wikipedia.org)
Chk1 has a regulatory role in the spindle checkpoint however the relationship is less clear as compared to checkpoints in other cell cycle stages. (wikipedia.org)
These studies suggest Chk1 depletion can lead to defects in the spindle checkpoint resulting in mitotic abnormalities. (wikipedia.org)
DNA damage induces the activation of Chk1 which facilitates the initiation of the DNA damage response (DDR) and cell cycle checkpoints. (wikipedia.org)
Notably, we found that the expression of the CHK1 phosphatase PP1α is increased in Spi1/PU.1-overexpressing cells. (oncotarget.com)

Although highly preliminary, the findings suggest that different tumor biological factors may predict response to different chemotherapy regimens with distinct mechanisms of action. (lu.se)
Research in the Andreassen Laboratory at Cincinnati Children's Hospital Medical Center focuses on DNA damage response mechanisms, including cell cycle checkpoint signaling and DNA repair by homologous recombination (HR), that maintain genome stability and thereby prevent tumorigenesis. (cincinnatichildrens.org)
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)
In different immune cell types, each MiT family member is shown to play distinct or redundant roles and we expect that there is far more to learn about their functions and regulatory mechanisms in host defense and inflammatory responses. (molcells.org)
[ 6 ] These events lead the cancer cell to escape normal cell growth and control mechanisms, to avoid system control mechanisms (ie, immunologic surveillance), and to establish a nutrient supply. (medscape.com)
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)
Comparing these transcriptional responses provides a greater understanding of the mechanisms cells use in the differentiation between types of DNA damage and the potential consequences of different sources of damage. (biomedcentral.com)
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)
Summing up, we are trying to understand the mechanisms by which microRNAs regulate mammalian cell cycle and DNA replication in normal and pathological conditions. (nii.res.in)
These results are consistent with previous studies and demonstrate that our methodology is effective for studying cooperative mechanisms in the cell cycle. (biomedcentral.com)
For chemotherapy drugs, one of the best characterized resistance mechanisms is overexpression of MDR1 , a cell membrane transporter that causes efflux of certain drugs (eg, vinca alkaloids, taxanes, anthracyclines). (msdmanuals.com)
Small Indels in the Androgen Receptor Gene: Phenotype Implications and Mechanisms of Mutagenesis. (medscape.com)

The genes TP53 and CHEK2 are also associated with an increased risk of breast cancer. (biotopics.co.uk)
CHEK2 is not only a breast cancer susceptibility gene but also a multi-organ cancer susceptibility gene [15]. (termedia.pl)

The protein product of the murine double minute gene 2 (mdm-2) plays a central role in the regulation of p53. (lu.se)
These multiple layers of regulation enable p53 to execute cellular responses that are appropriate for specific cellular states and environmental conditions. (nih.gov)
This negative regulation of DNA-PKcs by depleting PIG3 seemed to take place at the translational level but not at the levels of transcription or protein degradation. (ijbs.com)
These results provide a new insight into the mechanism of PIG3's functioning in DNA damage signaling and the regulation network of cellular DNA-PKcs expression homeostasis. (ijbs.com)
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)

Recent studies indicate that ATM is activated primarily in response to double strand breaks and may be considered a caretaker of the genome. (bmj.com)
They are a direct consequence of mis-repaired DNA double strand breaks (DNA-DSBs) due to defects in the DNA damage response associated with exposure to topoisomerase-II poisons such as etoposide. (ibecbarcelona.eu)

These findings establish a mechanism for co-targeting DNA damage-induced cell cycle checkpoints in combination with repair of cisplatin-DNA lesions in vivo using RNAi nanocarriers, and motivate further exploration of ASL as a generalized strategy to improve cancer treatment. (nature.com)
Cancer cells that are defective in p53 function are deficient in their ability to transcriptionally upregulate the CDK inhibitor p21 after genotoxic stress. (nature.com)
The clonal evolution and cancer stem cell theories of cancer formation, have been used to explain tumour heterogeneity. (scienceopen.com)
While the clonal evolution theory argues that all cells within a tumour possess this ability, the cancer stem cell theory argues that only a few cells (cancer stem cells or CSCs) within the tumour possess this ability to seed the tumour in a different location. (scienceopen.com)
Data supporting the cancer stem cell theory is accumulating. (scienceopen.com)
Molecular genetic studies of familial cancer syndromes identified and defined the recessive nature of tumor suppressor genes and resolved the paradox of why tumors arising in such families exhibited an autosomally dominant pattern of inheritance. (scienceopen.com)
Cell plasticity and heterogeneity in cancer. (scienceopen.com)
and the cancer stem cells phenotype can vary substantially between patients. (scienceopen.com)
Here the current status and progresses of cancer stem cells theory is illustrated and via providing a panoramic view of cancer therapy, we addressed the recent controversies regarding the feasibility of cancer stem cells targeted anti-cancer therapy. (scienceopen.com)
Gene expression profiling of pancreatic cancer cells identifies more than 200 genes commonly regulated by STAT3 and oncogenic KRAS. (bvsalud.org)
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)
Conclusions Our findings demonstrate that therapeutic targeting of LDHC may inhibit tumor growth while releasing the anti-tumor immune response in breast cancer, and warrant further in-depth investigation. (bmj.com)
In turn, as a result of research into the abnormal cancer cell, the basic understanding of the cell has greatly improved. (medscape.com)
[ 1 ] Identifying candidate precursors or enabling genes may pave the way for cancer screening, as with the ret proto-oncogene and medullary thyroid carcinoma . (medscape.com)
A few gene therapy trials now target head and neck cancer, which comprises only 4% of all cancers but has a dismal prognosis in advanced stages. (medscape.com)
Cancer is characterized by uncontrolled growth and division of a cell with extension beyond the normally limiting basement membrane and through the boundaries of normal cells. (medscape.com)
This is the multihit theory of tumorigenesis, in which a series of multiple triggering events in the genetic and cellular makeup of a cell ultimately cause cancer. (medscape.com)
p21 and other tumor suppressor genes' inactivation are therefore most likely involved in the first steps of the cancer model, with later stages possibly involving protooncogene activation and inflammation. (medscape.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)
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)
Design Glutathione peroxidase 4 (GPx4), which is considered the master regulator of ferroptosis, was genetically altered in murine models for hepatocellular carcinoma (HCC) and colorectal cancer (CRC) to analyse the effect of ferroptosis on tumour cells and the immune tumour microenvironment. (bmj.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)
Notably, changes including elevated levels of expression of Kras and mmu-miR-155 and the repression of Socs1 were observed following genotoxic damage, reflecting induction of a cancer-prone phenotype. (biomedcentral.com)
These results suggest genotoxic damage may induce a unique cancer-prone phenotype and processes mimicking activated B cell response to antigenic agents, as well as the normal B cell maturation processes. (biomedcentral.com)
Failure to properly repair this damage can lead to detrimental health effects, such as uncontrolled cell death and cancer formation. (biomedcentral.com)
Therefore, we selected 53BP1 as an attractive candidate gene for breast cancer susceptibility. (biomedcentral.com)
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)
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)
Based on the heterogeneity within a specific tumor type, a combination of genomic alterations defines the cancer subtype, biologic behavior, and in some cases, response to therapeutics. (hindawi.com)
Consideration of tumor heterogeneity is therefore important in the critical analysis of gene associations in cancer. (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)
hRad9 is a cell cycle checkpoint gene that is up-regulated in breast cancer. (biomedcentral.com)
Immunoblotting with and without dephosphorylation was used to define the protein isolated from breast cancer cells. (biomedcentral.com)
Increased hRad9 protein was observed in breast cancer cells nucleus compared to non-tumor epithelium. (biomedcentral.com)
Finding of hyperphosphorylated forms of hRad9 in the nucleus of cancer cells is in keeping with its function in ameliorating DNA instability, whereby it inadvertently assists tumor growth. (biomedcentral.com)
To further examine the role of hRad9 in breast cancer cells, we now report on the histologic expression of the hRad9 protein and its different molecular forms in primary breast cancer and normal tissues. (biomedcentral.com)
A few gene therapy trials now target head and neck cancer, which makes up only 4% of all cancers but has a dismal prognosis in advanced stages. (medscape.com)
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)
Загальні відомості про терапію злоякісних новоутворень Curing cancer requires eliminating all cells capable of causing cancer recurrence in a person's lifetime. (msdmanuals.com)
The ideal drug would target only cancer cells and have no adverse effects on normal cells. (msdmanuals.com)
Cytotoxic drugs damage DNA and kill many normal cells as well as cancer cells. (msdmanuals.com)
In contrast, other drugs (eg, DNA cross-linkers, also known as alkylating agents) have a linear dose-response relationship, killing more cancer cells at higher doses. (msdmanuals.com)
In addition, many cancer treatments damage the heart, and some cancer types increase risk for developing CVD (4). (cdc.gov)

Ionizing radiation can cause DSBs, as well as other DNA lesions, and has been shown to disrupt many cellular functions. (biomedcentral.com)
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)

Therefore, we are trying to understand the independent mechanism by which mammalian cells effectively inhibit the replication machinery during stress preventing it from drifting towards a catastrophic path of genomic instability. (nii.res.in)

In the context of DNA damage, p53 is thought to be a decision-making transcription factor that selectively activates genes as part of specific gene expression programmes to determine cellular outcomes. (nih.gov)

The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. (affbiotech.com)

These genetic alterations result in either activation or inactivation of specific gene functions that contribute to the process of carcinogenesis. (bmj.com)

The same gene called Rad27 was identified in budding yeast by Carr and associates. (wikipedia.org)

These transcriptional factors belong to the basic helix-loop-helix-leucine zipper (bHLH-LZ) transcription factor family and bind the E-box DNA motifs in the promoter regions of target genes to enhance transcription. (molcells.org)

Lowering KRAS activity in established tumors promotes immune infiltration, but with a limited antitumor effect, whereas combining KRAS/MEK inhibition with immune checkpoint blockade achieves durable regression in preclinical models. (bvsalud.org)
Interestingly, the miR378a causal network also indicated inhibition of the immune response in LDHC positive cells. (bmj.com)
Here we expand the concept of synthetic lethality in ATM-null CLL and address the question of whether ATM-null deficient CLL cells can be targeted by inhibition of the ATR protein that governs responses to post-replicative damage and co-operates with ATM. (birmingham.ac.uk)
These genetic aberrations may cause loss of growth inhibition in normally quiescent cells and result in carcinogenesis [ 5 ]. (biomedcentral.com)

The results of our phenotype analysis also indicate that it is more likely that a panel of tumor biological factors instead of only one single factor may be needed for better prediction of chemotherapy response. (lu.se)
I went through this process for biological process and cellular component lists separately, but there was some overlap between these gene lists. (github.io)
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)
Identifying the essential components in a specific biological process and detecting the associations among these components in response to various conditions are important for understanding cellular functions. (biomedcentral.com)
Subcommittee report on biological indicators of organ damage. (cdc.gov)

It coordinates cell cycle checkpoint activation, replication fork stability, restart and origin firing to maintain genome integrity. (dundee.ac.uk)

We now recognize that tumor suppressor genes regulate diverse cellular activities, including cell cycle checkpoint responses, detection and repair of DNA damage, protein ubiquitination and degradation, mitogenic signaling, cell specification, differentiation and migration, and tumor angiogenesis. (scienceopen.com)
RNA sequencing of sorted germinal center B cells revealed that STAT3 promotes proliferation and B cell processes of the germinal center but does not directly regulate viral gene expression. (bvsalud.org)
2) How does chromatin modification at sites of DNA damage regulate DNA repair and transcription? (mdanderson.org)

Knockdown of Rad9 in prostate tumor cells correlates with reduction of tumorigenicity in nude mice [ 16 ]. (biomedcentral.com)

Specifically, we discuss how the interaction of p53 with DNA and chromatin affects gene expression, and how p53 post-translational modifications, its temporal expression dynamics and its interactions with chromatin regulators and transcription factors influence cell fate. (nih.gov)
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)
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)

This complex is recruited by checkpoint protein RAD17 to the sites of DNA damage, which is thought to be important for triggering the checkpoint-signaling cascade. (avivasysbio.com)
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)

High tumor proliferation has previously been associated with response to chemotherapy. (lu.se)

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)
DNA damage, from cellular metabolism or exogenous sources, and unscheduled oncogene expression both lead to replicative stress and represent major sources of genetic instability. (oncotarget.com)

Human Rad 9 ( hRad9 ) was originally identified as a structural homologue of yeast schizosaccharomyces pombe rad 9 , which can partially rescue the sensitivity of rad 9 null yeast to hydroxyurea, radiation damage and the associated checkpoint defects [ 1 ]. (biomedcentral.com)
The theoretical basis for marrow failure includes primary defects in or damage to the stem cell or the marrow microenvironment. (medscape.com)

Thus, whether MLL fusions compromise the recognition and/or repair of DNA damage remains unanswered. (ibecbarcelona.eu)

In the present study, the potential mechanism of PIG3 participation in the DNA damage response induced by ionizing radiation (IR) was investigated in multiple cell lines with depleted expression of PIG3 transiently or stably by the small interference RNA and lentivirus-mediated shRNA expression strategies. (ijbs.com)
The DNA double-strand break (DSB) is considered to be the most severe type of DNA damage induced by ionizing radiation, and this form of DNA damage must be repaired immediately to prevent cell death. (ijbs.com)
Current standard of care involves maximal surgical resection followed by concurrent therapy with radiation and the DNA alkylating agent temozolomide. (bmj.com)
Here we compare transcriptional responses to physiological DNA breaks with responses to genotoxic DNA damage induced by ionizing radiation. (biomedcentral.com)
One such damage source is ionizing radiation (IR), which can be generated from both natural and man-made sources including radon gas and medical devices and procedures. (biomedcentral.com)
Repair kinetics of etoposide- and ionizing radiation-induced DSBs was identical in WT, MA4- and A4M-expressing cells, as revealed by flow cytometry, by immunoblot for γH2AX and by comet assay. (ibecbarcelona.eu)
1993. Protective effects of chlorogenic acid, curcumin and beta-carotene against gamma-radiation-induced in vivo chromosomal damage. (cdc.gov)
Radiation, carcinogenesis and DNA alterations. (cdc.gov)
External insults (eg, infections, radiation, drugs) may disrupt stem cell homeostasis in marrow environment, leading to altered growth. (medscape.com)

Enhanced phosphorylation of p53 by ATM in response to DNA damage. (reactome.org)
The C-terminal domain of hRad9 contains phosphorylation sites and hyperphosphorylation of hRad9 occurs in response to DNA damage [ 10 ]. (biomedcentral.com)

Methyalation of this gene could promote homeostasis by regulating gonad development processes. (github.io)
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)
Double strand (ds) DNA breaks are a form of DNA damage that can be generated from both genotoxic exposures and physiologic processes, can disrupt cellular functions and can be lethal if not repaired properly. (biomedcentral.com)
We identified a central lymphocyte-specific transcriptional response common to both physiologic and genotoxic breaks, which includes many lymphocyte developmental processes. (biomedcentral.com)
Although a number of approaches have been used to predict gene functions and interactions, tools that analyze the essential coordination of functional components in cellular processes still need to be developed. (biomedcentral.com)
These results provide a global view of the cell cycle and the method can be used to discover the dynamic coordination properties of functional components in other cellular processes. (biomedcentral.com)

The theories both point to the existence of cells within a tumour that are capable of initiating the tumour in a different location. (scienceopen.com)
This was foiled by tumour cell plasticity, a phenomenon whereby a non-CSC spontaneously de-differentiates into a CSC. (scienceopen.com)
The tumour suppressor p53 has a central role in the response to cellular stress. (nih.gov)
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)
A tumour - also known as a neoplasm - is a collection of cells which have grown into a defined shape. (biotopics.co.uk)
However, alterations to tumour suppressor genes can lead to the development of tumours. (biotopics.co.uk)
Instead, GPx4-associated ferroptotic hepatocyte death causes a tumour suppressive immune response characterised by a CXCL10-dependent infiltration of cytotoxic CD8 + T cells that is counterbalanced by PD-L1 upregulation on tumour cells as well as by a marked HMGB1-mediated myeloid derived suppressor cell (MDSC) infiltration. (bmj.com)

To determine whether Rad1 functions to maintain genomic stability and prevent tumor development, we generated Mrad1 mutant mice by gene targeting. (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)
3) How does the cell protect genome stability in response to DNA replication stress? (mdanderson.org)

Examples of these genes are BRCA1 and BRCA2 in breast and ovarian cancers. (hindawi.com)

These genome wide transcriptional responses are very tightly regulated and complex. (biomedcentral.com)
While it is known that genotoxic agents, such as IR, activate transcriptional programs involved in maintaining the integrity of the genome, we also want to investigate whether or not the genotoxic breaks could affect lymphocyte-specific maturation transcriptional responses similar to those we observed following RAG-induced physiological DSBs. (biomedcentral.com)
By comparing the transcriptional responses to both types of DNA damage, we can compare the similarities in the responses to damage as well as the differences induced by genotoxic damage. (biomedcentral.com)

Our findings revealed that different genetic backgrounds of HCT116 and HT29 cell lines resulted in divergent responses to the combination treatments. (frontiersin.org)
The AT locus was mapped to the chromosomal region 11q22-23 using genetic linkage analysis in the late 1980s and the causative gene was identified by positional cloning several years later. (bmj.com)
Genetic deletion of STAT3 in B cells of CD19cre/+Stat3f/f mice reduced peak latency approximately 7-fold. (bvsalud.org)
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)

Checkpoint kinases (Chks) are protein kinases that are involved in cell cycle control. (wikipedia.org)
Rad1 plays crucial roles in DNA repair and cell cycle checkpoint control, but its contribution to carcinogenesis is unknown. (biomedcentral.com)
Obviously this is the result of cell division, but the speed or rate of division can be a problem, and the cell division may not be under control like ordinary cells. (biotopics.co.uk)
Malignant tumours are cancerous growths and because their cell division is not subject to normal control they may grow quite fast and can sometimes spread to other parts of the body. (biotopics.co.uk)
genes that normally control the way cells divide, grow and develop. (biotopics.co.uk)
Thus, RPS27L modulates DNA damage response and functions as a part of the control switch to determine cell fate to DNA damage-p53 response. (figshare.com)
Aberrations in microRNA activity has been linked to loss of cell cycle and replication control and this has led to oncogenic functions (thereby called oncomirs) being ascribed to them. (nii.res.in)

10 Genes that, when activated, contribute to the carcinogenesis are generally termed proto-oncogenes. (bmj.com)

The concept has now been extended to embrace synthetic lethal drug sensitivity, such as that observed with PARP inhibitors in combination with DNA-damaging chemotherapy in a variety of BRCA defective tumors 10 . (nature.com)

Recently, numerous gene expression and molecular interaction experiments have been reported in Saccharomyces cerevisiae , and these have enabled systematic studies. (biomedcentral.com)

abstract = "Ataxia Telangiectasia and Rad3 related (ATR) is one of the main regulators of the DNA damage response. (dundee.ac.uk)

It is a tumor suppressor gene, involved in DNA DSB repair through the process of homologous recombination [16]. (termedia.pl)

Her research is focused on understanding how cells respond to DNA damage and safeguard the integrity of the genome. (mdanderson.org)

Furthermore, haploinsufficient mammary epithelial cells illustrated misaligned chromosomes and abnormal segregation. (wikipedia.org)

An image depicting head and neck squamous cell carcinoma in vitro can be seen below. (medscape.com)
Head and neck squamous cell carcinoma in vitro (cell culture). (medscape.com)

2021). Examination of the C. gigas kinome found several serine/threonine-protein kinases in eggs and embryos, with some gene expression changes in response to abiotic stress (Epelboin et al. (github.io)

Here we compare the response of developing B cells to both physiologic and genotoxic DSBs. (biomedcentral.com)

The TP53-binding protein (53BP1) has been shown to influence TP53-mediated transcriptional activation, thus playing a pivotal role in DNA damage signalling. (biomedcentral.com)

It is known that replication factors are downregulated during stress and we have observed that cullin 4-based ubiquitin ligase mediate the proteolysis of Mcm10, a protein essential for the initiation and elongation phases of DNA replication. (nii.res.in)

Anatomy28

Organisms6

Diseases12

Chemicals and Drugs110

Analytical, Diagnostic and Therapeutic Techniques and Equipment21

Phenomena and Processes91

Disciplines and Occupations1

Information Science3

Health Care3

Kinase16

Apoptosis20

Proteins16

Progression12

Arrest10

Mutations14

Pathway8

Pathways8

Mutation7

Chk114

Mechanisms13

CHEK22

Regulation5

Double strand breaks2

Cancer51

Lesions2

Genomic instability1

Activates1

Regulator1

Inactivation1

Budding yeast1

Target genes1

Inhibition4

Biological5

Genome integrity1

Regulate3

Rad91

Transcription3

RAD172

Proliferation1

Replicative stress2

Defects2

Repair of DNA damage1

Radiation9

Phosphorylation2

Processes6

Tumour7

Stability3

BRCA11

Transcriptional responses3

Genetic4

Control7

Proto-oncogenes1

BRCA1

Saccharomyces1

Abstract1

Homologous recombination1

Integrity1

Chromosomes1

Head and neck squamous cell carc2

Protein kinases1

DSBs1

TP531

Elongation1