• 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)
  • 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)
  • HR comprises different pathways: gene conversion (GC) that accurately repair the lesion by copying the homologous sequence, single strand annealing (SSA) or break induced replication (BIR) that can both lead to loss of genetic information. (cea.fr)
  • These areas are approached by investigations that span from structural characterization of single molecules, macromolecular interactions and supramolecular assemblies, over mapping of molecular pathways in different model organisms, to whole genome sequencing of human pathogens. (ki.se)
  • These alterations can take the form of epigenetic modifications, point mutations, translocations, amplifications or deletions and modify gene functions in ways that deregulate cellular signalling pathways leading to the cancer phenotype. (bmj.com)
  • These 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)
  • 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)
  • Even as the nature of the exact cell in which Merkel cell carcinoma oncogenesis occurs is controversial, there is strong support for the notion that Merkel cell carcinoma results from of one of two distinct pathways. (medscape.com)
  • Cell division is intimately connected to an evolutionarily conserved DNA damage response (DDR), which involves DNA repair pathways that reverse DNA lesions, as well as checkpoint pathways that inhibit cell cycle progression while repair occurs. (unimi.it)
  • 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)
  • 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)
  • We shall consider each subtype in turn describing genes and pathways of oncogenesis and how these relate to prognosis and treatment response. (springer.com)
  • Numerous E3 ubiquitin ligases, which facilitate the ubiquitination of specific substrates, have been shown to control G1/S. In this chapter, we will discuss components in the ubiquitin proteasome system that are implicated in G1/S control, how these enzymes are interconnected, gaps in our current knowledge, and the potential role of these pathways in the cancer cycle and disease proliferation. (intechopen.com)
  • Cells have evolved with conserved recombination mediated genome editing pathways as a mean for repairing DSBs and restarting replication forks, thus allowing genome duplication to continue [ 8 ]. (springeropen.com)
  • 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)
  • Unrepaired or incorrectly repaired DNA damage may lead to loss of heterozygosity, mutations, deletions, genomic rearrangements and chromosome loss. (cea.fr)
  • 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)
  • 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)
  • Mutations in the genes that encode these proteins can result in disease. (cshl.edu)
  • In addition, it has to be emphasized, that stromal cells, lymphocytes and endothelial cells in the clinical samples are essential as internal positive tissue controls especially for carcinomas with TP53 mutations causing absence and loss of p53 expression in the tumour cells. (nordiqc.org)
  • 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)
  • Multiple mutations affecting embryonic development have been induced by chemical and insertional mutagenesis resulting in the identification of genes with important roles in development in Drosophila [ 23 - 25 ]. (biomedcentral.com)
  • These studies reveal that recurrent somatic mutations occur in only a handful of genes, with an overall mutational burden of roughly 1-2 per Mb. (springer.com)
  • hnRNPs affect several aspects of the cell cycle by recruiting, splicing, and co-regulating certain cell cycle control proteins. (wikipedia.org)
  • hnRNP serves a variety of processes in the cell, some of which include: Preventing the folding of pre-mRNA into secondary structures that may inhibit its interactions with other proteins. (wikipedia.org)
  • 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)
  • 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)
  • It seems now clear that posttranslational modification of both DNA repair and checkpoint proteins is of importance for the regulation of their activities but how these modifications are regulated and how they affect the activity of the proteins only begins to be described. (cea.fr)
  • 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)
  • The M. leprae genome contains 1614 open reading frames coding for functional proteins, and 1310 pseudogenes corresponding to 41% of the genome, approximately. (bvsalud.org)
  • Deletion or mutation of genes coding for Ku70 or Ku80 proteins results in a highly radiosensitive phenotype [10]. (termedia.pl)
  • 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)
  • 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)
  • In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons. (arigobio.cn)
  • Defining the functional relationships between proteins is critical for understanding virtually all aspects of cell biology. (thebiogrid.org)
  • The origin recognition complex (ORC) is a group of proteins involved with every cell division event in our cells. (cshl.edu)
  • In the mammalian genome, this group of proteins assembles at tens of thousands of sites all at once, ensuring each chromosome is copied precisely once per cell division. (cshl.edu)
  • T-antigen hijacks other proteins from the infected cell to replicate the virus genome. (cshl.edu)
  • Over the next few decades researchers would use SV40 replication to discover dozens of cellular proteins that are necessary for human cell genome replication. (cshl.edu)
  • The ORC complex proteins are kept near each other in liquid compartments in the nucleus and recruit proteins such as CDC6 and other proteins that control when to commit the cell to divide. (cshl.edu)
  • Not only are ORC proteins involved in DNA replication, but they also help divide the chromosomes equally into the two new cells. (cshl.edu)
  • In contrast, the thermally sensitive population exhibited higher basal levels of heat shock proteins and had three times fewer changes in gene expression overall. (frontiersin.org)
  • Transcripts found in unfertilized oocytes also encoded a large number of proteins implicated in cell adherence, tight junction and focal adhesion, suggesting high complexity in terms of structure and cellular interactions in embryos prior to midblastula transition (MBT). (biomedcentral.com)
  • The oocyte is loaded with maternal mRNAs and proteins that control the cell maintenance and fate and the formation of the body plan prior to the onset of zygotic genome expression [ 3 , 4 ]. (biomedcentral.com)
  • Like Rb protein, many of the proteins encoded by tumor suppressor genes act at specific points in the cell cycle. (medscape.com)
  • Keratinocytes isolated from Mrad1 +/- mice had significantly more spontaneous DNA double strand breaks, proliferated slower and had slightly enhanced spontaneous apoptosis than Mrad1 +/+ control cells. (biomedcentral.com)
  • The effects of heterozygous deletion of Mrad1 on proliferation and apoptosis of keratinocytes is different from those resulted from Mrad9 heterozygous deletion (from our previous study), suggesting that Mrad1 also functions independent of Mrad9 besides its role in the Mrad9-Mrad1-Mhus1 complex in mouse cells. (biomedcentral.com)
  • 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)
  • It is also involved in cell cycle arrest and apoptosis [17]. (termedia.pl)
  • 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)
  • 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)
  • It coordinates cell cycle checkpoint activation, replication fork stability, restart and origin firing to maintain genome integrity. (dundee.ac.uk)
  • Genome integrity is constantly threatened by DNA lesions. (cea.fr)
  • Concerning the maintenance of genome integrity, recent data highlight the importance of nuclear architecture. (cea.fr)
  • 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 key interests lie within the field of genome integrity and variation, cell division, regulation of gene expression, protein turnover and signal transduction. (ki.se)
  • Thus, ATR couples DNA replication with mitosis and preserves genome integrity by enforcing an S/G 2 checkpoint. (elsevierpure.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)
  • 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)
  • Here we present that hereditary instability, awareness to medications impairing different mobile procedures and genome-wide transcriptional misregulation in could be partly or totally suppressed if SWR1 isn't formed (as well as the ATPase-dead the nucleosome remodelling activity of SWR1 impacts chromatin integrity due to an attempt to displace H2A with Htz1 in the lack of the last mentioned. (irjs.info)
  • In particular, ubiquitin-mediated degradation is critically important at transition points where it provides directionality and irreversibility to the cell cycle, which is essential for maintaining genome integrity. (intechopen.com)
  • Hence, although the repair of DSBs is crucial for the maintenance of genome integrity the process of repair need to be well regulated and closely monitored. (springeropen.com)
  • Regardless of how DSBs are formed, faithful repair of these breaks are absolutely essential for maintenance of genome integrity. (springeropen.com)
  • In spite of the mutagenicity associated with NHEJ, its fast kinetics has a unique role in safeguarding genome integrity, particularly by suppressing chromosomal translocations [ 15 ]. (springeropen.com)
  • p53 suppression of genes is often carried out by a number of these lincRNAs, which in turn have been shown to act though hnRNP K. Through physical interactions with these molecules, hnRNP K is targeted to genes and transmits p53 regulation, thus acting as a key repressor within the p53-dependent transcriptional pathway. (wikipedia.org)
  • 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)
  • Disruption of normal regulation of the cell cycle can lead to diseases such as cancer. (medlineplus.gov)
  • 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)
  • Regulation of the DNA damage response by cyclin-dependent kinases / C. Trovesi, N. Manfrini, M. Falcettoni, M.P. Longhese. (unimi.it)
  • The limited changes in gene regulation suggest that individuals have reduced genome plasticity to tolerate thermal fluctuations and consequently may not have enough energy to repair damage and resume cellular homeostasis at extreme temperatures. (frontiersin.org)
  • Regulation of gene expression plays a central role in embryonic development. (biomedcentral.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)
  • Here we show that cells transactivate the mitotic gene network as they exit the S phase through a CDK1 (cyclin-dependent kinase 1)-directed FOXM1 phosphorylation switch. (elsevierpure.com)
  • During normal DNA replication, the checkpoint kinase ATR (ataxia-telangiectasia and Rad3-related) is activated by ETAA1 to block this switch until the S phase ends. (elsevierpure.com)
  • In response to DNA damage, a synthetic lethal relationship exists between the cell cycle checkpoint kinase MK2 and the tumor suppressor p53. (nature.com)
  • Checkpoint kinase 2 (CHEK2), a cell cycle checkpoint regulator gene, codes for a kinase protein activated in response to radiation and other agents that cause breaks in the DNA. (termedia.pl)
  • 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)
  • Cdk1 (cyclin-dependent kinase 1), also known as p34Cdc2 (cell division control protein kinase 2) depends on cyclin A and B and is triggered by a positive feedback loop at the end of G2 phase, which is the key event that initiates mitotic entry. (arigobio.cn)
  • 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)
  • 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)
  • In response to ionizing radiation, hnRNP C partially localizes to the site of DNA damage, and when depleted, S-phase progression of the cell is impaired. (wikipedia.org)
  • Here, we demonstrate that the dNTPase activity of SAMHD1 is regulated by acetylation, which promotes cell cycle progression in cancer cells. (oncotarget.com)
  • Here we show that cell cycle progression through mitosis following double-stranded DNA breaks leads to the formation of micronuclei, which precede activation of inflammatory signalling and are a repository for the pattern-recognition receptor cyclic GMP-AMP synthase (cGAS). (nature.com)
  • Inhibiting progression through mitosis or loss of pattern recognition by stimulator of interferon genes (STING)-cGAS impaired interferon signalling. (nature.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)
  • Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression. (arigobio.cn)
  • In addition, the absence of Htz1 affects DNA replication and cell cycle progression and causes lethality or sickness in combination with S-phase checkpoint mutants [21]. (irjs.info)
  • The eukaryotic cell cycle comprises a series of events, whose ordering and correct progression depends on the oscillating activity of cyclin-dependent kinases (Cdks), which safeguard timely duplication and segregation of the genome. (unimi.it)
  • The most relevant articles summarising existing knowledge on RCC genomics, including tumour cell evolution and progression, were selected for this review. (springer.com)
  • During cell growth and proliferation, ubiquitin plays an outsized role in promoting progression through the cell cycle. (intechopen.com)
  • Progression through the cell cycle is driven by the oscillating activity of Cyclin Dependent Kinases (CDKs). (intechopen.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)
  • 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)
  • Also see Merkel Cell Tumors of the Head and Neck and Merkel Cell Carcinoma and Rare Appendageal Tumors . (medscape.com)
  • Deep sequencing and gene centric common insertion sites landscapes in resistant tumors (separate Excel file). (bace-signal.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)
  • Destruction of cyclin B during metaphase results in inactivation of Cdk1, allowing mitotic exit and cell division. (arigobio.cn)
  • Recombination between homologous sequences is a fundamentally important process both in meiosis and in mitotic cells. (brandeis.edu)
  • To this end we have expressed the site-specific HO endonuclease in meiotic cells so that we can compare recombination events at the same loci where we have used HO to stimulate recombination in mitotic cells. (brandeis.edu)
  • 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)
  • 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)
  • Thus, schizogony challenges some basic paradigms about DNA replication control, while gametogenesis demands a speed of DNA replication and cell division that is unprecedented in eukaryotic gametogenesis. (europa.eu)
  • BRCA1 in particular causes G2/M cell cycle arrest in response to DNA damage via the CHEK1 signaling cascade. (wikipedia.org)
  • Through these genes, hnRNP is necessary to induce cell-cycle arrest in response to DNA damage by ionizing radiation. (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)
  • Within regions of copy-number gain, CRISPR/Cas9 targeting of both expressed and unexpressed genes, as well as intergenic loci, led to significantly decreased cell proliferation through induction of a G2 cell-cycle arrest. (broadinstitute.org)
  • Activation of p21 or p16 therefore causes cell cycle arrest. (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)
  • 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)
  • 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)
  • To determine whether Rad1 functions to maintain genomic stability and prevent tumor development, we generated Mrad1 mutant mice by gene targeting. (biomedcentral.com)
  • H2A.Z/Htz1 is also involved in genome stability. (irjs.info)
  • However, Cdks have to be carefully regulated, because even an excess of their activity can affect genome stability. (unimi.it)
  • DNA double strand breaks (DSBs) result as a consequence of the disassembly of the DNA double helix leading to the disruption of the stability of the genome. (springeropen.com)
  • 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)
  • However, in the midst of this process of genome editing, small deletions and insertions might be introduced at the junction site. (springeropen.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)
  • 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)
  • Marked p53 accumulation (at least 20-50% of the cells stained) largely reflects an underlying mutation. (nordiqc.org)
  • 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)
  • 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)
  • hnRNP C is a key regulator of the BRCA1 and BRCA2 genes. (wikipedia.org)
  • BRCA1 and BRCA2 are crucial tumor-suppressor genes which are strongly implicated in breast cancers when mutated. (wikipedia.org)
  • Examples of these genes are BRCA1 and BRCA2 in breast and ovarian cancers. (hindawi.com)
  • This gene is involved in the repair of DNA double-strand breaks by homologous recombination and it functionally complements Chinese hamster irs1, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents. (cancerindex.org)
  • It is a tumor suppressor gene, involved in DNA DSB repair through the process of homologous recombination [16]. (termedia.pl)
  • There is increasing evidence that Cdks are involved in the DDR, in particular in DNA repair by homologous recombination and in activation of the checkpoint response. (unimi.it)
  • 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)
  • A p53 dependent checkpoint pathway prevents re-replication. (nii.res.in)
  • Non-homologous end joining (NHEJ), which does not depend upon sequence homology, is the key repair pathway during the G0/G1 stages of the cell cycle [ 10 ]. (springeropen.com)
  • DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.com)
  • Heterogeneous nuclear ribonucleoproteins (hnRNPs) are complexes of RNA and protein present in the cell nucleus during gene transcription and subsequent post-transcriptional modification of the newly synthesized RNA (pre-mRNA). (wikipedia.org)
  • Here we compare transcriptional responses to physiological DNA breaks with responses to genotoxic DNA damage induced by ionizing radiation. (biomedcentral.com)
  • 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)
  • These genome wide transcriptional responses are very tightly regulated and complex. (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)
  • Via dephosphorylation, calcineurin is the enzyme responsible for activating nuclear factor of activated T-cells (NF-AT), a T cell transcriptional regulatory factor. (medindex.am)
  • Required in higher cells for entry into S-phase and mitosis. (arigobio.cn)
  • 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)
  • Ataxia telangiectasia (AT) is a rare multisystem, autosomal, recessive disease characterised by neuronal degeneration, genome instability, and an increased risk of cancer. (bmj.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)
  • p53 binding decreases its control with cell proliferation and increases genetic instability, leading to neoplastic transformation. (nordiqc.org)
  • Mutated p53 shows impaired DNA-binding and, consequently, release from cell cycle checkpoint control following DNA damage, thereby increasing genomic instability and promoting gene amplification. (nordiqc.org)
  • K405R mutant expressing cancer cells have reduced G1/S transition and slower proliferation compared to wildtype. (oncotarget.com)
  • Collectively, these findings suggest that SAMHD1 acetylation enhances its dNTPase activity and promotes cancer cell proliferation. (oncotarget.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)
  • 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)
  • We performed genome-scale loss-of-function screens in 33 cancer cell lines to identify genes essential for proliferation/survival and found a strong correlation between increased gene copy number and decreased cell viability after genome editing. (broadinstitute.org)
  • Notably, the G1/S boundary represents a major barrier to cell proliferation and is universally dysfunctional in cancer cells, allowing for the unbridled proliferation observed in malignancy. (intechopen.com)
  • Inactivation of tumor suppressor genes, whose products normally provide negative control of cell proliferation, contributes to malignant transformation in various cell types. (medscape.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)
  • There are now near-complete ancient genome sequences for three pathogens of considerable historical interest - pre-modern bubonic plague (Yersinia pestis), smallpox (Variola virus) and cholera (Vibrio cholerae) - and for three equally important endemic human disease agents - Mycobacterium tuberculosis (tuberculosis), Mycobacterium leprae (leprosy) and Treponema pallidum pallidum (syphilis). (bvsalud.org)
  • 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)
  • Broad Genomics Platform sequences a whole human genome every four minutes. (broadinstitute.org)
  • We have been fascinated by the process of yeast mating-type gene switching, in which cells replace about 700 bp of Ya or Y-specific DNA sequences at the MAT locus by recombining with one of two donor loci, called HMLDescription: image3 and HMRa. (brandeis.edu)
  • [ 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)
  • 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)
  • 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)
  • Cells are constantly exposed to stresses from cellular metabolites as well as environmental genotoxins. (biomedcentral.com)
  • 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)
  • Physiologic dsDNA breaks are generated in a variety of normal cellular functions, including the RAG endonuclease-mediated rearrangement of antigen receptor genes during the normal development of lymphocytes. (biomedcentral.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)
  • Genomic Copy Number Dictates a Gene-Independent Cell Response to CRISPR/Cas9 Targeting. (broadinstitute.org)
  • By examining single-guide RNAs that map to multiple genomic sites, we found that this cell response to CRISPR/Cas9 editing correlated strongly with the number of target loci. (broadinstitute.org)
  • These observations indicate that genome targeting by CRISPR/Cas9 elicits a gene-independent antiproliferative cell response. (broadinstitute.org)
  • This effect has important practical implications for the interpretation of CRISPR/Cas9 screening data and confounds the use of this technology for the identification of essential genes in amplified regions. (broadinstitute.org)
  • The major event of MBT was the activation of a large group of histones and other genes that modify chromatin structure preceding massive gene expression changes. (biomedcentral.com)
  • The next most prevalent aberrations include a cohort of chromatin-modifying genes with diverse roles including PBRM1 , SETD2 , BAP1 , and KMD5C . (springer.com)
  • The higher incidence of ccRCC in male patients may partially be accounted by mono-allelic inactivation of the chromatin remodelling gene, KDM5C on the X chromosome [ 6 ]. (springer.com)
  • 13 Genome Plasticity and B Cell, University of Paris-Sud, Centre National de la Recherche Scientifique, Cancer Institute Gustave Roussy, Villejuif, France. (jci.org)
  • 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)
  • Although SAMHD1 is expressed ubiquitously throughout the human body, the molecular mechanisms regulating its enzymatic activity and function in non-immune cells are relatively unexplored. (oncotarget.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)
  • Control mechanisms establish this order by dictating when a cell transitions from one phase to the next. (elsevierpure.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)
  • consequently cells have evolved a variety of mechanisms to repair double-strand breaks (DSBs). (brandeis.edu)
  • Recombination based mechanisms are crucial for both the repair and tolerance of DNA damage that vexes both strands of the double helix [ 9 ]. (springeropen.com)
  • Although most studies of ancient genomes have focused on vertebrates, particularly archaic humans, newer technologies allow the capture of microbial pathogens and microbiomes from ancient and historical human and non-human remains. (bvsalud.org)
  • There have been efforts to sequence the genomes of additional ancient pathogens, with the potential to broaden our understanding of the infectious disease burden common to past populations from the Bronze Age to the early 20th century. (bvsalud.org)
  • Numerous genes transcribed in oocytes are involved in multiple aspects of cell maintenance and protection, including metabolism, signal perception and transduction, RNA processing, cell cycle, defense against pathogens and DNA damage. (biomedcentral.com)
  • 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)
  • 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)
  • These genetic alterations result in either activation or inactivation of specific gene functions that contribute to the process of carcinogenesis. (bmj.com)
  • 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)
  • With a degree in Genetics, you will be playing a vital part in the development of genetic engineering and the decoding of the human genome. (leeds.ac.uk)
  • Changes in the p53 gene is one of the most common genetic changes associated with cancer, being implicated in a wide range of tumour types. (nordiqc.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)
  • In this review, we consider what is currently known of the genetic landscape of the commonest subtypes of renal cell cancer (RCC). (springer.com)
  • Failure to repair DSBs can lead to unwanted consequences, such as loss of genetic information, chromosomal rearrangements and even cell death. (springeropen.com)
  • 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)
  • A poorly understood feature of these responses is the delayed onset (days), in contrast to the acute DNA-damage responses that occur in minutes to hours. (nature.com)
  • d) investigation of cell-cycle checkpoints and replicative responses to the changing environment in the human host and to antimalarial drugs. (europa.eu)
  • HER2 is an upstream regulator of cyclin D1 and p27, and its overexpression leads to the deregulation of the G1/S checkpoint. (wikipedia.org)
  • 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)
  • This powerful alteration in nucleosome framework offers a molecular system to modify transcription, gene silencing, chromosome segregation and DNA fix. (irjs.info)
  • Using whole-genome sequencing of OS, we found features of TP53 intron 1 rearrangements suggesting a unique mechanism correlated with transcription. (oncotarget.com)
  • Desogestrel binds intracellular progesterone receptors in progesterone responsive tissue and the resultant complex interacts with DNA and results in either gene transcription or gene repression. (medindex.am)
  • 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)
  • Finally, findings from The Cancer Genome Atlas (TCGA) validation cohort confirmed a significant association of high Nek1 expression with a reduced disease-free survival. (uni-frankfurt.de)
  • Data were then validated using The Cancer Genome Atlas (TCGA) dataset. (uni-frankfurt.de)
  • Clear cell, papillary cell, and chromophobe renal cell carcinomas (RCCs) have now been well characterised thanks to large collaborative projects such as The Cancer Genome Atlas (TCGA). (springer.com)
  • Cold Spring Harbor Laboratory (CSHL) President and CEO Bruce Stillman and other CSHL scientists have been working for decades to understand the intricacies of ORC, DNA replication, and cell division. (cshl.edu)
  • I lead the University's Genome Engineering Laboratory (www.westmingenlab.uk), providing a sustainable platform for student innovation, short-term internships, and skill development to support their research ambitions. (westminster.ac.uk)
  • In 2017, I transitioned into a full-time role and established the Genome Engineering Laboratory (www.westmingenlab.uk). (westminster.ac.uk)
  • Immune cells are removed from the body and sent to a laboratory, where they're modified to recognize prostate cancer cells. (healthline.com)
  • Two SNPs in X-Ray Repair Cross Complementing 2 gene (XRCC2) rs2040639 and interferon gamma (IFNG) rs2069705 genes were found to be associated with ARSR. (cancerindex.org)
  • Deoxyribonucleotide triphosphates (dNTPs) are the precursors of DNA synthesis, and their strict balance is critical for proper DNA replication and repair in cells [ 1 ]. (oncotarget.com)
  • DNA damage caused by these genotoxins can be efficiently fixed by DNA repair in cooperation with cell cycle checkpoints. (biomedcentral.com)
  • Rad1 plays crucial roles in DNA repair and cell cycle checkpoint control, but its contribution to carcinogenesis is unknown. (biomedcentral.com)
  • Failure to properly repair this damage can lead to detrimental health effects, such as uncontrolled cell death and cancer formation. (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)
  • Of even greater excitement is Bindra's comprehensive library of DNA repair inhibitor and damaging agents. (yale.edu)
  • We have focused a lot of attention on yeast mating-type gene switching ( MAT switching) as an example of DSB repair that we can study in great detail. (brandeis.edu)
  • MAT switching is an example of a repair process called gene conversion. (brandeis.edu)
  • In case of DNA damage, p53 arrests the cell cycle until repair has taken place. (nordiqc.org)
  • Driven by a profound interest in the nuclear events that influence human cell health and disease, I dedicated four years to serving as a European Framework for DNA Repair Postdoctoral Research Fellow. (westminster.ac.uk)
  • However, erroneous repair of DSBs can lead to chromosomal rearrangements and loss of heterozygosity, which in turn can also cause cancer and cell death. (springeropen.com)
  • In addition, these alterations affect 3 principal categories of genes, as follows: proto-oncogenes, tumor suppressor genes, and DNA repair genes. (medscape.com)
  • 3 , 4 The ATM gene is located at 11q22-23, spans 184 kb of genomic DNA, and has 66 exons. (bmj.com)
  • Feng et al established in 2008 that approximately 80% of Merkel cell carcinomas in the Northern hemisphere occur after genomic integration by a ubiquitous skin commensal virus, Merkel cell polyoma virus (MCPyV). (medscape.com)
  • The most common non-clear cell renal cancers have also undergone genomic profiling and are characterised by distinct genomic landscapes. (springer.com)
  • Experiments with Ku70/80 knocked out mice indicate that NHEJ is important for genome maintenance [8]. (termedia.pl)
  • Change in localisation depends on the checkpoint kinases Tel1ATM and Mec1ATR and has a positive effect on spontaneous recombination. (cea.fr)
  • hnRNPs also play a role in DNA damage response in coordination with p53. (wikipedia.org)
  • 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)
  • Ataxia Telangiectasia and Rad3 related (ATR) is one of the main regulators of the DNA damage response. (dundee.ac.uk)
  • 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)
  • Here we compare the response of developing B cells to both physiologic and genotoxic DSBs. (biomedcentral.com)
  • It has been reported that Ku-DNA binding inhibitors modulate the DNA damage response in response to DNA DSB [11]. (termedia.pl)
  • These results, together with the level of sensitivity of to medicines causing DNA damage during DNA replication [16], [17], suggest a role for Htz1 in the DNA damage response by replicative stress. (irjs.info)
  • Precis: Pulsed high doses versus sustained low doses of the p53-MDM2 inhibitor HDM201 elicit a pro-apoptotic response from wild-type p53 cancer cells, offering guidance to current clinical trials with this and other drugs that exploit the activity of p53. (bace-signal.com)
  • The p53 gene is a tumour suppressor gene located on the short arm of chromosome 17 (17p13.1). (nordiqc.org)
  • The Von Hippel-Lindau ( VHL ) tumour suppressor gene undergoes bi-allelic knockout in the vast majority of clear cell RCCs. (springer.com)
  • Transcriptome profiling of the early stages in Atlantic cod revealed the presence of transcripts involved in patterning and development of tissues and organs long before activation of the zygotic genome. (biomedcentral.com)
  • Degradation of maternal transcripts and zygotic genome activation is characterized by striking changes in the transcriptome profiles. (biomedcentral.com)
  • As a consequence, the synthesis and release of Th1- (T helper 1) and Th2- (T helper 2) type cytokines, and other inflammatory mediators from T-cells and mast cells are blocked and the expression of signals essential for the activation of inflammatory T-lymphocytes is inhibited. (medindex.am)
  • Transcriptomic analyses provide an efficient approach to explore the temporal gene expression profiles in embryos and to search for the developmental regulators. (biomedcentral.com)
  • Microarray analyses detected a suite of master developmental regulators that control differentiation and maintenance of diverse cell lineages. (biomedcentral.com)
  • We report a study of early Atlantic cod development that used a genome-wide oligonucleotide microarray to examine the composition and putative roles of polyadenylated transcripts. (biomedcentral.com)
  • Besides the existence of 9-1-1 heterotrimer in K562 and 293 human cells, a significant amount of hRad1 also exists in monomeric form, but monomeric hRad9 and hHus1 were not detectable in a study by Karnitz's group [ 10 ] and in our unpublished experiments in 293 human cells. (biomedcentral.com)
  • M. leprae is an obligate intracellular microorganism with a marked Schwann cell tropism and is the only human pathogen capable of invading the superficial peripheral nerves. (bvsalud.org)
  • The National Human Genome Research Institute's Talking Glossary provides information about the cell cycle . (medlineplus.gov)
  • In November 2022, Broad's Genomics Platform sequenced its 500,000th whole human genome, a mere four years after sequencing its 100,000th. (broadinstitute.org)
  • Remarkably little is known about Plasmodium cell cycles, despite a wealth of knowledge on the subject in human cells. (europa.eu)
  • Malaria parasites replicate inside the cells of their human host via 'schizogony', which is fundamentally different from conventional binary fission - the replication mode used by most cells from human cells to yeast cells. (europa.eu)
  • This takes a period of ~24 hours when the parasite is inside human red blood cells. (europa.eu)
  • Normal (wild type - WT) p53 is accumulated in damages cells, e.g., in virus infections, where the protein is bound (e.g., to protein E6 of human papilloma virus) and prevented from break down. (nordiqc.org)
  • Immunofluorescent staining of human cell line. (bdbiosciences.com)
  • Flow cytometric analysis of H2AX (pS139) expression on human peripheral blood mononuclear cells (Right Panel). (bdbiosciences.com)
  • 4 - 7 The ATM gene encodes a nuclear phosphoprotein of approximately 350 kDa (3056 amino acids) and is ubiquitously expressed. (bmj.com)
  • As a guideline for an accurate p53 IHC test more than 20% of germinal centre B-cells must show a weak to moderate nuclear staining reaction, while less than 10% of the mantle zone B-cells should be demonstrated in tonsil. (nordiqc.org)
  • In appendix, dispersed epithelial cells in the basal parts of the crypts must show a weak to moderate nuclear staining reaction, while the luminal epithelial cells must be negative. (nordiqc.org)
  • For example, the TP53 gene, located on chromosome 17, encodes a 53-kd nuclear protein that functions as a cell cycle checkpoint. (medscape.com)
  • 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)
  • hnRNP K is rapidly induced after DNA damage by ionizing radiation. (wikipedia.org)
  • Moreover, STING loss prevented the regression of abscopal tumours in the context of ionizing radiation and immune checkpoint blockade in vivo . (nature.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)
  • Nek1 knockdown (KD) sensitized both cell lines to ionizing radiation following a single dose irradiation and more pronounced in combination with a 6 h fractionation (3 × 2 Gy) regime. (uni-frankfurt.de)
  • My work on the "Gene Editors of the Future" was highlighted in SDG report of the University on 2021. (westminster.ac.uk)