Repair and checkpoint damage cell cycle checkpoint gene. Medical search. Frequent questions

RT can directly induce cancer cell death through various mechanisms, such as apoptosis, necrosis, and autophagy. (nature.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)
RESULTS: ETS1 overexpression increased hyperoxia-induced cell viability, glucose consumption, lactate production, and NADPH levels and reduced inflammation and apoptosis in A549 cells. (bvsalud.org)
Cell apoptosis was investigated by a flow cytometry assay, and apoptosis related proteins Bcl-2, cleaved-caspase 3 and 9 were analyzed by a western blot assay. (bvsalud.org)
If cells containing damaged DNA were to divide, the errors would be transmitted to daughter cells, generating genomic instability and resulting in tumorigenesis or apoptosis . (tocris.com)
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)
We further analyzed genes affected by PMS2 expression and observe the apoptosis-related TMS1 gene to be significantly upregulated whereas anti-apoptotic BCL2A1 was downregulated. (oncotarget.com)
These results demonstrate a functional role for PMS2 to protect against PCa progression by enhancing apoptosis of PCa cells. (oncotarget.com)
Compound 51 inhibited the proliferation of 13 out of 15 cancer cell lines with IC50 values between 0.27 and 6.9 muM, which correlated with the complete suppression of retinoblastoma phosphorylation and the onset of apoptosis. (proteopedia.org)
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 encoded protein can phosphorylate and activate several proteins involved in the inhibition of DNA replication and mitosis, and can promote DNA repair, recombination, and apoptosis. (sitoolsbiotech.com)
The TP53 gene is also capable of stimulating apoptosis of cells containing damaged DNA. (medscape.com)
TP53 activates the expression of genes involved in apoptosis, cell cycle regulation (p21), and MDM2. (medscape.com)
Cancer genetics, DNA damage response, apoptosis, cell cycle My current research is focused on two transcription factors that respond to DNA damage and play important roles in regulating tumor development. (mdanderson.org)
The first project focuses on E2F1, a regulator of genes important for cell cycle progression and apoptosis. (mdanderson.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)
If a cell has an error in its DNA that cannot be repaired, it may undergo self-destruction ( apoptosis ). (medlineplus.gov)
Apoptosis is a common process throughout life that helps the body get rid of cells that no longer work or that it doesn't need. (medlineplus.gov)
Apoptosis protects the body by removing genetically damaged cells that could lead to cancer, and it plays an important role in the development of the embryo and the maintenance of adult tissues. (medlineplus.gov)
A successful therapy must therefore eliminate these cells known to be highly resistant to apoptosis. (hindawi.com)
In this paper, we describe the metabolic changes as well as the mechanisms of resistance to apoptosis occurring in cancer cells and cancer stem cells, underlying the connection between these two processes. (hindawi.com)
1. Disrupted systems include pro to-oncogenes, tumor suppressor genes, and regulators of apoptosis. (ctsqena.com)
2. If DNA repair is not possible, p53 induces apoptosis. (ctsqena.com)
3. B cells that would normally undergo apoptosis during somatic hypermutation in the lymph node germinal center accumulate, leading to lymphoma. (ctsqena.com)
The study also demonstrates that mice with a high degree of chromosomal instability and defective programmed cell death (apoptosis), two hallmarks of cancer, rarely develop tumors. (rdworldonline.com)
Whether or not a tumor develops depends on the moment of the cell cycle in which the damage occurs, which repair pathways components are affected, and which others are impaired in terms of apoptosis and cell cycle arrest", explains the North-American Travis H. Stracker, head of the "Genomic Instability and Cancer" group and an expert in DNA repair pathways and its implications on human health. (rdworldonline.com)
Next, they combined them with other mutations affecting cell cycle checkpoints or apoptosis until they hit upon the combinations that are sufficient to initiate tumorigenesis or to generate certain types of tumors. (rdworldonline.com)
Such proteins activate programmed cell death (apoptosis) or cell cycle arrest (senescence). (rdworldonline.com)
NIMA (never-in-mitosis gene A)-related kinase 1 (Nek1) is shown to impact on different cellular pathways such as DNA repair, checkpoint activation, and apoptosis. (uni-frankfurt.de)
Stably transduced doxycycline (Dox)-inducible Nek1 shRNA HeLa cervix and siRNA-transfected HCT-15 colorectal carcinoma cells were irradiated in vitro and 3D clonogenic radiation survival, residual DNA damage, cell cycle distribution, and apoptosis were analyzed. (uni-frankfurt.de)

Oncologica's Next generation sequencing platform captures 764 of the leading anti-cancer targeted medicine drug combinations and immunotherapies via analysis of actionable genomic mutations across 505 genes. (businesswire.com)
166 actionable mutations were detected across 36 genes linked to 17 off label targeted therapy protocols and 111 clinical trials. (businesswire.com)
Most patients had 3 or more actionable mutations affecting key cancer regulatory networks including mitogenic signalling pathways, DNA-damage repair pathways and cell cycle checkpoints. (businesswire.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)
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)
Unrepaired or incorrectly repaired DNA damage may lead to loss of heterozygosity, mutations, deletions, genomic rearrangements and chromosome loss. (cea.fr)
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)
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)
However, mutations in p53 can result in abnormal p53 proteins that fail to stop cell division if the cell's DNA is damaged. (texasgateway.org)
This results in an increased number of mutations, leading to abnormal daughter cells. (texasgateway.org)
Even when all of the cell cycle controls are fully functional, a small percentage of replication errors (mutations) will be passed on to the daughter cells. (texasgateway.org)
Mutations of this gene are associated with Seckel syndrome. (utsouthwestern.edu)
However, cancer cells overcome these controls, in particular by acquiring genetic mutations leading to the activation of oncogenes (pten, myc) or loss of tumor suppressors (p53) [ 1 ]. (hindawi.com)
The researchers utilized mice carrying mutations in key DNA repair genes involved in cancer. (rdworldonline.com)
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)

Furthermore, inflammatory mediators released by irradiated dying cells can attract and regulate immune cells in the tumor microenvironment (TME), further killing cancer cells. (nature.com)
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)
Checkpoint control kinases is a term used to describe a group of enzymes that regulate progression of a cell through the cell cycle. (tocris.com)
Cancer results from unchecked cell division caused by a breakdown of the mechanisms that regulate the cell cycle. (texasgateway.org)
These compounds generally penetrate cell membranes, act on specific target proteins in cells, regulate intracellular signaling pathways, and cause some changes in cell phenotype. (chemscene.com)
The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway evaluation suggested that furthermore to Wnt and changing growth aspect (TGF) signaling pathways, that have been reported in response to follicle formation broadly, another mixed band of signaling pathways that regulate lipid synthesis and fat burning capacity, like the phosphatidylinositol signaling program and glycerolipid signaling and fat burning capacity, are Gemzar biological activity in charge of follicle formation also. (clinical-research-informatics.com)
Notable examples are genes from two cell cycle checkpoint pathways - CHEK1 and CHEK2 - which regulate a broad variety of DNA repair processes. (technologynetworks.com)
2) How does chromatin modification at sites of DNA damage regulate DNA repair and transcription? (mdanderson.org)
Genes that suppress carcinogenesis have been classified as gatekeepers that regulate cellular proliferation and cell death and as caretakers that are primarily encode DNA repair proteins required for the maintenance of genome integrity ( 15 ). (amegroups.org)

Through these BRCT specific interactions TOPBP1 mediates DNA damage repair, DNA replication, transcription, and mitosis. (wikipedia.org)
It effectively stimulates mitosis and extra cell division. (biotopics.co.uk)
DSBs are first detected and signaled by the DNA damage checkpoint that triggers cell cycle arrest, providing time for the cell to repair damaged chromosomes before entering mitosis. (cea.fr)
In addition cells have evolved a damage-sensing checkpoint system whereby the cells delay entry into mitosis until the break has been repaired. (brandeis.edu)
activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. (proteopedia.org)
regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. (proteopedia.org)
3.A.2 In eukaryotes, heritable information is passed to the next generation via processes that include the cell cycle and mitosis or meiosis plus fertilization. (texasgateway.org)
The G 2 gap phase further separates S-phase from mitosis, allowing for continued cell growth and maturation before cell division. (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)
additionally, at the finish of mitosis, CyclinB1 is prompted to degrade the complex, enabling cells to complete the replication cycle [10]. (rockinhibitor.com)

Cyclin-dependent kinases (CDKs) are serine/threonine protein kinases that act as key regulatory elements in cell cycle progression. (proteopedia.org)
Eukaryotic cells have developed exquisite mechanisms that monitor and coordinate cell cycle progression with repair of DNA damage to maintain genome integrity. (biomedcentral.com)
The CDK4-cyclinD complex normally phosphorylates the retinoblastoma protein (Rb protein), leading to release of the E2F transcription factor and cell cycle progression. (medscape.com)
For instance, DNA replication and DNA damage checkpoints delay cell cycle progression until each chromosome is fully replicated and physically intact. (rupress.org)
Accumulating evidence shows that cancer stem cells are key drivers of tumor formation, progression, and recurrence. (hindawi.com)
4, Cell cycle regulators mediate progression through the cell cycle {e.g., cyctin and cyclin-dependent kinase). (ctsqena.com)
For example, the cvclinD/CDK4 complex phosphorylates the retinoblastoma protein, which promotes progression through the G^S checkpoint. (ctsqena.com)
K, p53 regulates progression of the cell cycle from Gt to S phase, 1. (ctsqena.com)
Rb mutation results in const it utively free E2F, allowing progression through the cell cycle and uncontrolled growth of cells. (ctsqena.com)
Genomic stability relies around the precise execution of DNA replication, chromosome segregation, DNA repair and genomic monitoring mechanisms, and their integration with cell cycle progression and also other processes. (rockinhibitor.com)

For a cell to progress through the cycle and replicate, it must pass through checkpoints between phases to ensure that DNA is replicated correctly and that chromosomes segregate. (tocris.com)
Tight regulation of this process ensures that a dividing cell's DNA is copied properly, any errors in the DNA are repaired, and each daughter cell receives a full set of chromosomes. (medlineplus.gov)

DNA topoisomerase 2-binding protein 1 (TOPBP1) is a scaffold protein that in humans is encoded by the TOPBP1 gene. (wikipedia.org)
The TOPBP1 gene encodes a scaffold protein which facilitates interactions between different proteins at specific times and locations. (wikipedia.org)
It accomplishes these interactions with other protein partners through its breast cancer associated gene 1 C-terminus (BRCT) domains. (wikipedia.org)
TOPBP1 was first identified as a DNA damage protein through its association with BRCA1, which is a protein heavily implicated in breast cancer pathology. (wikipedia.org)
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)
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)
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)
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)
What does this gene/protein do? (cancerindex.org)
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 is found to possess 3' to 5' exonuclease activity, which may contribute to its role in sensing and repairing DNA damage. (avivasysbio.com)
It forms a checkpoint protein complex with RAD1 and HUS1. (avivasysbio.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)
Oestrogen enters target cells, and binds with a receptor protein. (biotopics.co.uk)
Resection is accompanied by the binding of replication protein A (RPA) to the 3' single-stranded overhangs, which helps recruiting the checkpoint complexes. (cea.fr)
ETS1 overexpression increased the mRNA and protein levels of Nrf2, HO-1, xCT, and GPX4 in hyperoxia-induced A549 cells and BPD mice. (bvsalud.org)
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)
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)
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)
The Rad1 protein, evolutionarily conserved from yeast to humans, exists in cells as monomer as well as a component in the 9-1-1 protein complex. (biomedcentral.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)
One culprit that has been identified is the p53 protein (coded for by the p53 gene), a major regulator at the G 1 checkpoint. (texasgateway.org)
All cancers start when a gene mutation gives rise to a faulty protein that plays a key role in cell reproduction. (texasgateway.org)
The change in the cell that results from the malformed protein may be minor-perhaps a slight delay in the binding of Cdk to cyclin or an Rb protein that detaches from its target DNA while still phosphorylated. (texasgateway.org)
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 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)
This kinase has been shown to phosphorylate checkpoint kinase CHK1, checkpoint proteins RAD17, and RAD9, as well as tumor suppressor protein BRCA1. (utsouthwestern.edu)
The protein encoded by this gene is a serine/threonine kinase and DNA damage sensor, activating cell cycle checkpoint signaling upon DNA stress. (sitoolsbiotech.com)
[ 1 ] His prediction was subsequently supported by the cloning of the retinoblastoma tumor suppressor gene ( RB1 ) and by functional studies of the retinoblastoma protein, Rb. (medscape.com)
Like Rb protein, many of the proteins encoded by tumor suppressor genes act at specific points in the cell cycle. (medscape.com)
For example, the TP53 gene, located on chromosome 17, encodes a 53-kd nuclear protein that functions as a cell cycle checkpoint. (medscape.com)
The p19ARF protein, which is encoded by the same locus as p16, also leads to cell cycle arrest by inhibiting the ability of MDM2 to inactivate TP53. (medscape.com)
The p16INK4A protein is a cell-cycle inhibitor that acts by inhibiting activated cyclin D:CDK4/6 complexes, which play a crucial role in the control of the cell cycle by phosphorylating Rb protein. (medscape.com)
The other project involves the study of a single nucleotide polymorphism (SNP) in the human p53 gene that results in either arginine (R) or proline (P) at position 72 of the p53 protein. (mdanderson.org)
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)
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)
That's because the absence of those proteins allows a third enzyme, called the Bloom syndrome protein (BLM), to not only resume the resection of DNA double-strand breaks, but go into repair overdrive, called "hyper-resection. (yale.edu)
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)
DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key component of the non-homologous end-joining (NHEJ) pathway, is involved in DNA double-strand break repair, immunocompetence, genomic integrity, and epidermal growth factor receptor signaling. (amegroups.org)
The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is the key component of the non-homologous end-joining (NHEJ) pathway for DNA double-strand break (DSB) repair and is required for cellular resistance to ionizing radiation (IR) ( 1 , 2 ). (amegroups.org)
Within this study, we further explored the role of MUS81 and CyclinB in regulating the therapeutic sensitivity of ovarian cancer.molecules have been measures by Western blotting, and pH2AX was used as an indicator of double-strand break repair.Western blotTotal protein was collected as previously described. (rockinhibitor.com)

10 Genes that, when activated, contribute to the carcinogenesis are generally termed proto-oncogenes. (bmj.com)
Proto-oncogenes are normal genes that, when mutated in certain ways, become oncogenes , genes that cause a cell to become cancerous. (texasgateway.org)
In addition, these alterations affect 3 principal categories of genes, as follows: proto-oncogenes, tumor suppressor genes, and DNA repair genes. (medscape.com)
This article briefly discusses tumor suppressor genes and then focuses on the role of proto-oncogenes in childhood cancer. (medscape.com)

Also see Merkel Cell Tumors of the Head and Neck and Merkel Cell Carcinoma and Rare Appendageal Tumors . (medscape.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)
Although carcinogenic roles for the INK4B, INK4C, INK4D, CIP1, KIP1, and KIP2 genes appear to be limited, INK4A is among the most commonly mutated genes in human tumors. (medscape.com)
Small tumors have a greater percentage of actively dividing cells than do large tumors. (msdmanuals.com)

To mediate these aspects of DNA repair, TOPBP1 was found to associate with Rad9, which forms a complex with Rad1 and Hus1, hereby termed the 9-1-1 DNA repair clamp. (wikipedia.org)
Knockdown of Rad9 in prostate tumor cells correlates with reduction of tumorigenicity in nude mice [ 16 ]. (biomedcentral.com)
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)

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)
Activation of p21 or p16 therefore causes cell cycle arrest. (medscape.com)
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)

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)
In all organisms, two different mechanisms are used to repair DSBs: Homologous recombination (HR) and non-homologous end joining (NHEJ). (cea.fr)
consequently cells have evolved a variety of mechanisms to repair double-strand breaks (DSBs). (brandeis.edu)
Through detailed characterization of fundamental molecular mechanisms of normal and perturbed cells, the theme strives to unravel information that increases the understanding of various diseases such as cancer and neurodegenerative, cardiovascular and inflammatory disorders. (ki.se)
The stem cell and developmental biology program at CMB is engaged in a broad range of basic research aimed at understanding the molecular mechanisms underlying diverse aspects of embryonic development and tissue regeneration. (ki.se)
If they find cells with damaged DNA, p53 will trigger repair mechanisms or destroy the cells, thus suppressing the formation of a tumor. (texasgateway.org)
Eventually, the pace of the cell cycle speeds up as the effectiveness of the control and repair mechanisms decreases. (texasgateway.org)
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)
The damage overcomes DNA repair mechanisms, but is not lethal. (ctsqena.com)
These results are consistent with previous studies and demonstrate that our methodology is effective for studying cooperative mechanisms in the cell cycle. (biomedcentral.com)

Moreover, in adults, Merkel cells undergo slow turnover and are replaced by cells originating from epidermal stem cells, not through the proliferation of differentiated Merkel cells. (medscape.com)
After Lef1 overexpressing plasmid and the vector were transfected into hyperoxia-induced MLE-12 cells, cell proliferation assays were carried out. (bvsalud.org)
Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). (proteopedia.org)
Inactivation of tumor suppressor genes, whose products normally provide negative control of cell proliferation, contributes to malignant transformation in various cell types. (medscape.com)
Cell proliferation involves the replication of all cellular contents with the required energy for this to happen. (hindawi.com)
To prevent aberrant cell proliferation, these pathways are tightly regulated. (hindawi.com)
This activation is necessary for both cell proliferation as well as glucose uptake and use. (hindawi.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)

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)
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)
Recently we used a modification of this system to study the mutation rate associated with DSB repair. (brandeis.edu)
DNA mismatch repair (MMR) enzymes act as proofreading complexes that maintains genomic integrity and MMR-deficient cells show an increased mutation rate. (oncotarget.com)
Unrepaired DNA lesions can lead to cell death, gene mutation and cancer. (biomedcentral.com)
If changes to the DNA nucleotide sequence occur within a coding portion of a gene and are not corrected, a gene mutation results. (texasgateway.org)
If a cell cannot reproduce, the mutation is not propagated and the damage is minimal. (texasgateway.org)
Occasionally, however, a gene mutation causes a change that increases the activity of a positive regulator. (texasgateway.org)
Germline mutation of one TP53 allele is found in patients with Li-Fraumeni syndrome who generally inherit a mutated TP53 gene from an affected parent. (medscape.com)

In this study, published in the journal Proceedings of the National Academy of Sciences (PNAS), the scientists postulate that the initiation of a tumor and the type and aggressivity of the same depend on a specific combination of defects in several processes that safeguard cell integrity, such as DNA repair pathways and cell cycle check-points. (rdworldonline.com)

TOPBP1 primarily regulates the DNA damage repair response through its ability to activate the damage response kinase, ataxia-telangiectasia mutated and RAD3-related (ATR). (wikipedia.org)
As a structure-specific endonuclease, MUS81 is involved in cell cycle regulation and regulates the DNA damage repair approach. (rockinhibitor.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)

Once recruited to DSB, these complexes get activated and induce the phosphorylation of numerous targets including transducing kinases, which subsequently phosphorylate downstream effectors to delay cell cycle and promote DNA repair. (cea.fr)
Additionally, the checkpoint kinases modify the chromatin surrounding DNA damages through phosphorylation of the H2A histone (H2AX in mammals). (cea.fr)
Although phosphorylation of H2A represents a major histone modification that functions in DNA repair, a growing body of literature has implicated additional histone modifications. (cea.fr)
The C-terminal domain of hRad9 contains phosphorylation sites and hyperphosphorylation of hRad9 occurs in response to DNA damage [ 10 ]. (biomedcentral.com)
EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. (proteopedia.org)
In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. (proteopedia.org)
Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. (proteopedia.org)
Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. (proteopedia.org)
We have discovered that E2F1 localizes to sites of both DNA double-strand breaks and UV-induced DNA damage and that this involves the phosphorylation of E2F1 by the ATM or ATR kinases. (mdanderson.org)
The physiological relevance of E2F1 in the DNA damage response is now being explored using a novel knock-in mouse model we developed that blocks E2F1 phosphorylation by ATM/ATR. (mdanderson.org)
In normal cells, glucose participates in cellular energy production through glycolysis as well as through its complete catabolism via the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). (hindawi.com)
Here, we report the association of Polo-like kinase (PLK) 3 expression and Caspase 8 T273 phosphorylation levels with survival among patients with cervical squamous cell carcinoma (CSCC) treated with CRT plus BT. (uni-frankfurt.de)
DNA-PKcs phosphorylation at the Thr2609 cluster region is particularly significant since it is critical for DSB repair and radioresistance ( 6 - 9 ). (amegroups.org)

Carcinogenesis is a multi-step process wherein abrogation of multiple cancer susceptibility genes leads to cancer development. (amegroups.org)

Immunotherapy mainly includes immune checkpoint inhibitors (ICIs), such as inhibitors of PD-1 (programmed cell death 1)/programmed cell death ligand 1 (PD-L1). (nature.com)
Linkage with immunotherapy and PARP inhibitors was identified in 44% of glioblastoma patients because of alterations in DNA-damage repair genes. (businesswire.com)
Another important class of tumor suppressor genes involved in cell cycle control and in the generation of human cancers is the cyclin-dependent kinase (CDK) inhibitors. (medscape.com)

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)
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)
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)
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)

Using synchronized cells undergoing recombination that is initiated at a specific site on a chromosome by an inducible endonuclease, we use physical monitoring techniques (Southern blots, PCR analysis) to follow the sequence of molecular events that occur in real time. (brandeis.edu)
We have shown that this regulation involves the action of a small Recombination Enhancer (RE) sequence that enables a donor on the left chromosome arm to recombine preferentially in MATa cells. (brandeis.edu)
Each chromosome harbors essential genes. (rupress.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)

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)

With the advent of improved immunohistochemical profiling, the tumor was reclassified as Merkel cell carcinoma because shared epithelial and neuroendocrine markers, along with ultrastructural features suggestive of neural crest origin, were observed in both the constituent tumor cell and the physiologic Merkel cell of the skin. (medscape.com)

We are interested in understanding at the molecular level how recombination occurs and what roles are played by the many proteins involved in DNA recombination, repair and replication. (brandeis.edu)
We saw that two of the genes which produce proteins involved in repairing damaged DNA work in opposite ways with respect to reproduction in mice. (technologynetworks.com)

TOPBP1 was found in complex with BRCA1 at sites independent from replication forks (i.e identified by the DNA replication clamp proliferating cell nuclear antigen) during normal S phase. (wikipedia.org)
When DNA damage was induced at higher levels by γ irradiation, there was an increase in TOPBP1/BRCA1 at sites away from replication forks. (wikipedia.org)
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)

DNA damage repair is initiated and maintained by two kinases, ataxia-telangiectasia mutated (ATM) and ATR, with ATR proving to be more important for maintaining the genome. (wikipedia.org)
Change in localisation depends on the checkpoint kinases Tel1ATM and Mec1ATR and has a positive effect on spontaneous recombination. (cea.fr)
Checkpoint control kinases function to halt the cell cycle at these critical points. (tocris.com)
Tocris offers the following scientific literature for Checkpoint Control Kinases to showcase our products. (tocris.com)
Cyclins and cyclin-dependent kinases (CDKs) form a complex which phosphorylates proteins that drive the cell through the cell cycle. (ctsqena.com)

DNA cannot be repaired (e.g. (ctsqena.com)

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)

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)
Zhao J, Kennedy BK, Lawrence BD, Barbie DA, Matera AG, Fletcher JA, Harlow E. NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription. (proteopedia.org)
As a transcription factor whose expression is increased by DNA damage, p53 blocks cell division at the G1 phase of the cell cycle to allow DNA repair. (medscape.com)
allows binding of transcription factors on outer DNA helix gene silencing (NO TRANSCRIPTION)! (freezingblue.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)
In contrast, cancer cells shift their metabolism toward lactate production even in the presence of oxygen [ 4 ], partly through genetic modifications that stabilize the transcription factor Hypoxia Inducible Factor (HIF) involved in the adaptation of the cells to hypoxia, under nonhypoxic conditions as well as generating an adaptive response to the hypoxic microenvironment (Figure 1 ). (hindawi.com)

Moreover, our studies demonstrate that E2F1 recruits chromatin-modifying enzymes to sites of damage to facilitate access to the DNA repair machinery. (mdanderson.org)
These findings indicate that E2F1 stimulates DNA repair through a non-transcriptional mechanism that functions in the context of chromatin. (mdanderson.org)
The regulation of DNA repair by the cell cycle is largely the result of chromatin alterations that happen through DNA replication, compression, and dissociation that permit cells to divide effectively [8]. (rockinhibitor.com)

promotes DNA double-strand break repair in distinct chromosomal contexts. (xenbase.org)

Thus the theme encloses expertise within bioinformatics, biophysics, biochemistry, molecular cell biology and genetics. (ki.se)
You'll establish your foundation of knowledge and expertise with a set of core modules including genetics, cell biology and biochemistry. (leeds.ac.uk)

4 - 7 The ATM gene encodes a nuclear phosphoprotein of approximately 350 kDa (3056 amino acids) and is ubiquitously expressed. (bmj.com)

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)
These models are being used to explore the roles of this human SNP in modulating cancer susceptibility and the response to DNA damaging agents, including chemotherapeutic drugs. (mdanderson.org)

How do cells sense DNA lesions? (xenbase.org)

However, alterations to tumour suppressor genes can lead to the development of tumours. (biotopics.co.uk)
These genetic alterations result in either activation or inactivation of specific gene functions that contribute to the process of carcinogenesis. (bmj.com)

Subcommittee report on biological indicators of organ damage. (cdc.gov)

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

Thirty SNPs of well-defined functional genes were investigated. (cancerindex.org)
A cooperative module pair is defined as two modules that significantly cooperate with certain functional genes in a cellular process. (biomedcentral.com)

NHEJ simply religates the broken ends whereas during HR a DNA break is repaired by copying homologous sequences present elsewhere in the genome. (cea.fr)
Recombination between homologous sequences is a fundamentally important process both in meiosis and in mitotic cells. (brandeis.edu)

TOPBP1/9-1-1 recruitment is conducted independent of ATRIP/ATR which serves as a regulatory mechanism that prevents both premature and non-specific activation of the DNA damage response pathway. (wikipedia.org)
In general, NHEJ is the preferred pathway in the G1 phase of the cell cycle, while HR is favored in S and G2 phases. (cea.fr)
DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.com)
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)

Even as they secrete neuropeptides, Merkel cells additionally express intermediate filaments characteristic of primitive and simple epithelia such as cytokeratin (CK) 8, CK18, and CK20. (medscape.com)
Additionally, in mice, they have successfully manipulated several key genes associated with these variants to extend their reproductive lifespan. (technologynetworks.com)

During the last decade, the non-random spatial arrangement of the genome into the nucleus of eukaryotic cells, as emerged as a key regulator of genome functions and notably of the propagation of a stable genome. (cea.fr)

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)

Order a complex pool of 30 siRNAs (siPOOL) for the specific gene knockdown of human gene ATR. (sitoolsbiotech.com)
Knocking out a specific gene (CHEK2) so that it no longer functions, and over-expressing another (CHEK1) to enhance its activity each led to an approximately 25 per cent longer reproductive lifespan in mice. (technologynetworks.com)

It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death. (tocris.com)
Furthermore, DNA-PKcs is required to prevent mitotic catastrophe in response to DNA damage ( 13 ). (amegroups.org)

Consequently, DNA repair processes have to be tightly regulated. (cea.fr)
These checkpoints may stop the cell cycle after DNA damage, loss of DNA replication or disruption of the mitotic spindle, in order for repair processes to take place. (tocris.com)
One of the critical processes monitored by the cell cycle checkpoint surveillance mechanism is the proper replication of DNA during the S phase. (texasgateway.org)
The team discovered that many of the genes involved are linked to processes of DNA repair. (technologynetworks.com)
If the cell detects errors in any of these phases, cell growth is halted and highly complex DNA repair processes are triggered. (rdworldonline.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 three dimensional organization of the genome in the nucleus, previously known to impact on gene expression, has recently emerged as a key regulator of DNA repair. (cea.fr)
is a direct negative regulator of the DNA-damage response. (xenbase.org)

The genes TP53 and CHEK2 are also associated with an increased risk of breast cancer. (biotopics.co.uk)

These include DNA damage repair, DNA replication, transcriptional regulation, and cell cycle checkpoint activation. (wikipedia.org)

It also plays a critical role in DNA replication initiation and regulation of the cell cycle. (wikipedia.org)
In normal cells, each stage of the cell cycle is tightly regulated, however in cancer cells many genes and proteins that are involved in the regulation of the cell cycle are mutated or over expressed. (tocris.com)
Disruption of normal regulation of the cell cycle can lead to diseases such as cancer. (medlineplus.gov)

Members of this kinase family have been shown to function in DNA repair and cell cycle checkpoint control following DNA damage. (bmj.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)
Rad1 plays crucial roles in DNA repair and cell cycle checkpoint control, but its contribution to carcinogenesis is unknown. (biomedcentral.com)
The loss of control begins with a change in the DNA sequence of a gene that codes for one of the regulatory molecules. (texasgateway.org)
Despite the redundancy and overlapping levels of cell cycle control, errors do occur. (texasgateway.org)
How do genes control the growth and division of cells? (medlineplus.gov)
A variety of genes are involved in the control of cell growth and division. (medlineplus.gov)
When the cell cycle proceeds without control, cells can divide without order and accumulate genetic errors that can lead to a cancerous tumor . (medlineplus.gov)

One study reported an increased survival benefit with simultaneous RT compared with sequential administration, 8 while another study found no significant difference between the two strategies, 9 possibly because simultaneous RT plus immunotherapy and the administration of an ICI before RT may kill cancer cells as well a substantial number of immune cells, leading to poor systemic response and toxic side effects. (nature.com)
They are fairly spherical structures composed of fibrous and muscle tissue, and they develop in response to oestrogen, which has the effect of thickening the lining of the uterine wall as part of the menstrual cycle. (biotopics.co.uk)
Specifically, the concepts of tumour heterogeneity, oncogene addiction, non-oncogene addiction, tumour initiating cells, tumour microenvironment, non-coding sequences and DNA damage response will be reviewed. (bmj.com)
In response to DNA damage, p53 slows the cell cycle and upregulales DNA repair enzymes. (ctsqena.com)
The paper points out that our understanding of which aspects of damage response promote tumorigenesis and where they play a role in the process needs to be investigated further because it shows that it has been generalized and that there is a lot of specifics that are not at all clear. (rdworldonline.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)

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

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)
Defects in this gene are a cause of Seckel syndrome 1. (sitoolsbiotech.com)

The potential regulatory relationship between ETS1 and Nrf2/HO-1 was examined by treating hyperoxia-induced A549 cells with the Nrf2 inhibitor ML385. (bvsalud.org)
Of even greater excitement is Bindra's comprehensive library of DNA repair inhibitor and damaging agents. (yale.edu)

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)
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)

We found that the more thermally tolerant population had greater plasticity of gene expression and had significantly more downregulated genes, which may provide more energy to repair damage associated with thermal stress and to maintain basic functions at these extreme temperatures. (frontiersin.org)
This method identifies cooperative module pairs that significantly influence a cellular process and the correlated genes and interactions that are essential to that process. (biomedcentral.com)

Anatomy24

Organisms6

Diseases12

Chemicals and Drugs112

Analytical, Diagnostic and Therapeutic Techniques and Equipment21

Phenomena and Processes93

Disciplines and Occupations1

Information Science3

Health Care3

Apoptosis34

Mutations16

Regulate9

Mitosis10

Progression10

Chromosomes2

Protein42

Proto-oncogenes4

Tumors4

Rad93

Arrest3

Mechanisms10

Proliferation9

Mutation10

Pathways and cell cycle1

Regulates the DNA damage repair2

Genomic instability1

Phosphorylation13

Susceptibility genes1

Inhibitors3

Ovarian4

Chromosome3

Genome Integrity1

Activates1

Tumor cell1

Proteins involved2

BRCA13

Kinases5

Cannot be repaired1

Related diseases1

Transcription6

Chromatin3

Double-strand break repair1

Genetics2

Encodes1

Cancer susceptibility2

Lesions1

Alterations2

Biological1

Biology3

Functional genes2

Homologous sequences2

Pathway5

Additionally2

Eukaryotic1

Instability1

Specific gene2

Mitotic catastrophe2

Processes7

Regulator2

CHEK21

Transcriptional1

Regulation of the cell cycle3

Control9

Response7

Integrity1

Defects2

Inhibitor2

BRCA2

Significantly2