• Genome instability (also genetic instability or genomic instability) refers to a high frequency of mutations within the genome of a cellular lineage. (wikipedia.org)
  • In humans, mutations that would change an amino acid within the protein coding region of the genome occur at an average of only 0.35 per generation (less than one mutated protein per generation). (wikipedia.org)
  • Mutations of proteins such as DNA polymerase or DNA ligase can lead to impairment of replication and lead to spontaneous chromosomal exchanges. (wikipedia.org)
  • These sites are called fragile sites, and can occur commonly as naturally present in most mammalian genomes or occur rarely as a result of mutations, such as DNA-repeat expansion. (wikipedia.org)
  • Failure to properly resolve RNA-DNA hybrids results in slower growth and the acquisition of mutations that can lead to antibiotic resistance. (northwestern.edu)
  • Fig. 3: Effects of Orc1 mutations on cell viability, complex formation, origin DNA binding and MCM loading. (nature.com)
  • Instability of the T-stretches has been reported in bacterial genomes ( 5 ) as being hot spots for mutations ( 5 ). (cdc.gov)
  • Changes to the structure of DNA can cause mutations and genomic instability, leading to cancer. (news-medical.net)
  • A number of recent studies have demonstrated that mutations in non-coding regions may have direct tumorigenic effects or lead to genetic instability. (frontiersin.org)
  • In this study, we present evidence for increased DNA damage and instability in cancer cells with RB pathway defects when RB1 mutations are induced. (bepress.com)
  • This study offers evidence that late-arising RB1 mutations can facilitate genome instability and cancer progression that are beyond the preexisting proliferative control deficit. (bepress.com)
  • We are investigating the impact of specific classes of gene mutations, such as ATM, BRCA1, and MYBL2 on genome integrity. (birmingham.ac.uk)
  • Mice with mutations in genes that regulate an important DNA replication complex, called the minichromosome maintenance complex or MCM, are susceptible to genomic instability and cancer. (nih.gov)
  • The researchers think that higher levels of micronuclei (fragments of chromosomes ejected from the main nucleus) caused by MCM mutations may trigger a specific DNA-sensing pathway called STING, which is the likely culprit behind the lethal inflammation in female embryos. (nih.gov)
  • Genome-caretaking mechanisms counteract the deleterious effects of DNA damage and are essential to prevent toxicity, mutations, genome instability, ageing and disease. (lumc.nl)
  • BML mutations thus result in defects in DNA repair and genomic instability in the somatic cells, predisposing the patients to cancer development. (medscape.com)
  • The nature of ionizing these effects can vary significant- fects, including DNA damage, chro- radiation ly, depending on the resulting dose mosomal aberrations, mutations, cell distribution or distribution of radionu- transformation, and cell killing (NRC, Ionizing radiation is a term used for clides throughout the body. (who.int)
  • RESULTS: All samples were analysed for DNA copy number changes, PIK3CA, KRAS, BRAF mutations, CIMP and microsatellite instability. (lu.se)
  • In a study of 450 CRC diagnosed under 50 years via the Ohio Colorectal Cancer Prevention Initiative, germline DNA analysis for mutations in 25 cancer susceptibility genes was done in addition to assessing microsatellite instability and/or immunohistochemistry for MMR deficiency. (cdc.gov)
  • Maintaining the genomic machinery is not a flawless process: DNA damage, genotoxic stresses, and defects in the repair pathways can all contribute to destabilizing the complex molecular networks keeping the genome intact. (biomedcentral.com)
  • Considering this intrinsic relationship, targeting cancer genomic instability with therapeutics has potential to improve the lives of cancer patients. (biomedcentral.com)
  • The ends of linear eukaryotic chromosomes are hidden in nucleoprotein structures called telomeres, and loss of the telomere structure causes inappropriate repair, leading to severe karyotypic and genomic instability. (nih.gov)
  • DNA repair and damage response contribute to genomic instability that accompanies tumor progression. (hindawi.com)
  • The accumulation of mutation in the genome led to genomic instability that accompanies the development of tumors [ 9 , 10 ]. (hindawi.com)
  • Genomic alterations in DNA repair genes also play a substantial role in response to chemotherapeutics underlying the genetics of multiple cancers, including breast, colorectal, ovarian, and lung cancer [ 11 - 13 ]. (hindawi.com)
  • The repair of damage to both DNA strands is particularly important in maintaining genomic integrity. (news-medical.net)
  • The Genome Structure Function section of the Institute of Cancer and Genomic Sciences investigates the fundamentals of the active information database that is our genome, in normal and disease states. (birmingham.ac.uk)
  • Female-biased embryonic death from inflammation induced by genomic instability. (nih.gov)
  • 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)
  • A hallmark of cancer is genomic instability. (mdanderson.org)
  • 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)
  • He works on elucidating mechanisms that generate antigen receptor diversity and, more generally, on mechanisms that generate and suppress genomic instability in mammalian cells, with a focus on the immune and nervous systems. (hoepli.it)
  • Owing to the genomic instability present in this disease, patients with Bloom syndrome show a much higher incidence of malignant neoplasms, which is the major cause of death in such patients. (medscape.com)
  • The overall result of the genomic instability in the proliferating cells is a high risk of malignancy, reduced fertility or infertility, B- and T-cell immunodeficiencies, and cutaneous manifestations, including photosensitivity, poikiloderma, and telangiectatic erythema. (medscape.com)
  • DSBs are the most dangerous, as they induce genomic instability. (bvsalud.org)
  • A high frequency of externally caused DNA damage can be one source of genome instability since DNA damage can cause inaccurate translesion DNA synthesis past the damage or errors in repair, leading to mutation. (wikipedia.org)
  • Another source of genome instability may be epigenetic or mutational reductions in expression of DNA repair genes. (wikipedia.org)
  • Because endogenous (metabolically-caused) DNA damage is very frequent, occurring on average more than 60,000 times a day in the genomes of human cells, any reduced DNA repair is likely an important source of genome instability. (wikipedia.org)
  • DNA replication errors are a major source of genome instability in all organisms. (thebiogrid.org)
  • Trinucleotide repeats are a source of genome instability, causing replication fork stalling, chromosome fragility, and impaired repair. (tufts.edu)
  • 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)
  • Such dichotomous kinetics implicate additional rate-limiting steps that are essential for DNA-damage-induced inflammation. (nature.com)
  • Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. (nature.com)
  • We encourage submissions of work that expands the mechanistic knowledge of DNA damage, repair, integrity, and stability as well as research that translates these concepts to ultimately target cancer at the bedside. (biomedcentral.com)
  • In this Collection, guest edited by Christopher Lord and Timothy Yap, we aim to highlight insights that expand upon our mechanistic knowledge of DNA damage, repair, integrity, and stability as well as research that leverages these concepts to ultimately target cancer at the bedside. (biomedcentral.com)
  • In addition to S-phase checkpoints, G1 and G2 checkpoints exist to check for transient DNA damage which could be caused by mutagens such as UV damage. (wikipedia.org)
  • An example is the Saccharomyces pombe gene rad9 which arrests the cells in late S/G2 phase in the presence of DNA damage caused by radiation. (wikipedia.org)
  • We previously reported that XPA mislocalized to the progerin-induced DNA double-strand break (DSB) sites, blocking DSB repair, which led to DSB accumulation, DNA damage responses, and early replication arrest in HGPS. (nih.gov)
  • Although it has been shown that DNA damaging agents activate a DNA damage response (DDR), little is known about the signaling of dysfunctional plant telomeres. (nih.gov)
  • These results uncover a new role for the CST complex in repressing the ATR-dependent DDR pathway in plant cells and show that plant cells use two different DNA damage surveillance pathways to signal telomere dysfunction. (nih.gov)
  • Previous studies have been identified of the importance of DNA repair and DNA damage response (DDR). (hindawi.com)
  • DNA repair can be divided into a set of mechanisms that identify and correct damage in DNA molecules. (news-medical.net)
  • Damage to DNA is caused by the incorporation of incorrect nucleotide bases during DNA replication and the chemical changes caused by spontaneous mutation or exposure to environmental factors such as radiation. (news-medical.net)
  • Direct reversal of DNA damage is a mechanism of repair that does not require a template and is applied to two main types of damage. (news-medical.net)
  • UV light induces the formation of pyrimidine dimers which can distort the DNA chain structure, blocking transcription beyond the area of damage. (news-medical.net)
  • The damage caused by alkylating agents reacting with DNA can also be repaired through direct reversal. (news-medical.net)
  • Nucleotide excision repair is a widespread mechanism for repairing damage to DNA and recognizes multiple damaged bases. (news-medical.net)
  • The process involves the recognition of damage which is then cleaved on both sides by endonucleases before resynthesis by DNA polymerase. (news-medical.net)
  • MCM8- and MCM9 Deficiencies Cause Lifelong Increased Hematopoietic DNA Damage Driving p53-Dependent Myeloid Tumors. (nih.gov)
  • He also holds the Canada Research Chair in Genome Damage and Instability Disease. (ucalgary.ca)
  • In the fission yeast Schizosaccharomyces pombe, the DNA damage response protein Brc1 binds phospho-histone H2A (γH2A)-marked chromatin during S-phase, but how Brc1 protects genome integrity remains unclear. (thebiogrid.org)
  • Cells with even one mutant copy of RB1 have increased basal levels of DNA damage and increased mitotic errors. (bepress.com)
  • Elevated levels of reactive oxygen species as well as impaired homologous recombination repair underlie this DNA damage. (bepress.com)
  • RB1 deletion in retinoblastoma protein pathway-disrupted cells results in DNA damage and cancer progression" Molecular and Cellular Biology Vol. 39 Iss. (bepress.com)
  • The anti-inflammatory properties of testosterone appear to protect male mouse embryos from certain types of DNA damage and inflammation that are fatal to female mouse embryos, according to a recent NIH-supported study. (nih.gov)
  • Treating pregnant mice with testosterone or ibuprofen improved the survival of female embryos with DNA damage and resulted in normal gender ratios among the mouse pups. (nih.gov)
  • The researchers also noted that the skewed gender ratios likely were not linked to all types of DNA replication and repair problems, but they may be limited to those that cause certain types of chromosomal damage. (nih.gov)
  • Our work shows how DNA damage and inflammation compromise the health of female mouse embryos," said Cornell's Dr. Schimenti. (nih.gov)
  • Her research is focused on understanding how cells respond to DNA damage and safeguard the integrity of the genome. (mdanderson.org)
  • 2) How does chromatin modification at sites of DNA damage regulate DNA repair and transcription? (mdanderson.org)
  • This department of LUMC researches topics related to the deleterious effects of DNA damage. (lumc.nl)
  • Tumours with defects in DNA damage repair mechanisms may be candidates for immunotherapy and other molecular therapeutics specifically targeting these defects. (lumc.nl)
  • To identify biomarkers of susceptibility to DNA damage to improve personalised cancer therapy. (lumc.nl)
  • To unveil roles of DNA damage and antibody effector pathways in inflammation. (lumc.nl)
  • Numerous cellular proteins detect DNA damage and induce senescence , a permanent change of state characterized by morphological and gene expression changes. (massgenomics.org)
  • In response to DNA damage, the cell activates nuclear DNA damage response (DDR) and the cytosolic DNA sensing protein (CDSP) pathways, the latter upon release of the DSBs to the cytosol. (bvsalud.org)
  • Cells without any functional ATM protein are hypersensitive to radiation and do not respond normally to DNA damage. (medlineplus.gov)
  • Mitochondrial quality control prevents accumulation of intramitochondrial-derived reactive oxygen species (mtROS), thereby protecting cells against DNA damage, genome instability, and programmed cell death. (lu.se)
  • Tumor initiation, progression, and evolution are often rooted in the malfunctioning of the checkpoints securing genome integrity. (biomedcentral.com)
  • Our lab has studied the effect of persistent ribonucleotides on genome integrity, using a combination of mutation accumulation lines, genetics, and in vitro reconstitution experiments. (northwestern.edu)
  • The mechanism is prone to error but protects genome integrity from possible chromosomal translocations that can occur through homologous recombination. (news-medical.net)
  • We are studying how genome integrity is preserved and the consequences of modifying the program of DNA replication. (umu.se)
  • Maintenance of genome integrity is of fundamental importance for cell survival and proliferation. (cam.ac.uk)
  • The way the DNA is structured, wrapped and read is fundamental to how and when the blueprint genes are read. (birmingham.ac.uk)
  • and tumors with chromosomal instability showing aneuploidy and amplifications of genes encoding receptor tyrosine kinases, the researchers said. (genomeweb.com)
  • in one study, 31 genes in breast CAFs, which were identified using Affymetrix Human Genome U133 Plus 2.0 and an empirical Bayesian model, were different from those in NFs ( 11 ). (spandidos-publications.com)
  • Inborn defects in genes controlling genome stability underlie inherited cancer predisposition and neurodegeneration whereas somatic loss of genome stability drives sporadic cancer, and is associated with ageing. (lumc.nl)
  • In addition, functional assays are being used and developed to assess pathogenicity of DNA variants in cancer-associated genes, and/or to predict outcomes of treatment. (lumc.nl)
  • Instead of activating DNA repair, the altered ATM protein allows variants to accumulate in other genes, which may cause cells to grow and divide in an uncontrolled way. (medlineplus.gov)
  • With roughly 30,000 genes in mammalian genomes, fection with a vector encoding MyoD (Tapscott et al. (lu.se)
  • explosion further, consider that a fictitious small genome with 2002) More recently and more dramatically, the potential for 260 genes would host the same number of combinations as cell state conversions is exemplified by the reprogramming of the number of atoms in the visible universe! (lu.se)
  • MCM8- and MCM9-deficient mice reveal gametogenesis defects and genome instability due to impaired homologous recombination. (nih.gov)
  • Problems with DNA replication and repair may also contribute to developmental defects and possibly to pregnancy loss, but the reasons for these problems are not well understood. (nih.gov)
  • It is also vital for counteracting disease, as genome instability is a hallmark of cancer, developmental defects, premature ageing and inflammation. (cam.ac.uk)
  • The researchers found heavy smokers-those who smoked 60 or more packs per year-have significantly more defects in their DNA than those who smoked 60 or fewer packs annually and non-smokers. (harvard.edu)
  • Thus, if MSH2 mutation screening results are negative, experts recommend DNA analysis of MSH6. (medscape.com)
  • This demonstrates the same principle as MSH2: If no mutation is identified, DNA analysis of MSH2 may be considered. (medscape.com)
  • As part of the multicenter, population-based Ohio Colorectal Cancer Prevention Initiative, tumor DNA was sequenced for 419 consecutive CRC cases undergoing standard universal tumor screening and germline genetic testing, and 46 patients with CRC known to have LS due to a germline mutation in a mismatch repair gene. (cdc.gov)
  • While whole exome sequencing (WES) remains popular and effective as a method of genetically profiling different cancers, advances in sequencing technology has enabled an increasing number of whole-genome based studies. (frontiersin.org)
  • Compared to whole genome sequencing (WGS), exome sequencing covers only the 1% of the genome that is translated into protein, greatly reducing the technical burden of data collection and analysis. (frontiersin.org)
  • performed the first whole-genome sequencing study on AML cells collected from a single patient. (frontiersin.org)
  • Greater understanding of the biology of cancer has led, over the years, to a deeper knowledge of the mechanisms safeguarding genome stability and the many ways in which these can fail. (biomedcentral.com)
  • 2022. Probing the mechanisms of two exonuclease domain mutators of DNA polymerase ε. (nih.gov)
  • Our research is defining the normal mechanisms of DNA replication and repair, with the aim of understanding how it is deregulated in cancer cells. (birmingham.ac.uk)
  • In this talk, I will present our recent findings that shed light on the molecular mechanisms of genome instability caused by aberrant processing of DNA -embedded ribonucleotides in mammalian cells. (cam.ac.uk)
  • His current research work involve systems biology of Huntington's disease, chromosome instability, non-coding RNAs in cancers, and cancer drug resistance mechanisms. (kgi.edu)
  • To obtain mechanistic understanding of genome surveillance mechanisms. (lumc.nl)
  • To improve diagnosis of pathologies caused by impaired genome surveillance mechanisms. (lumc.nl)
  • Recently, his group has developed senstive genome-wide approaches to identify mechanisms of DNA breaks and rearrangements in normal and cancer cells. (hoepli.it)
  • 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)
  • These proteins also prevent progression into mitosis by inhibiting the firing of late replication origins until the DNA breaks are fixed by phosphorylating CHK1 and CHK2, which results in a signaling cascade arresting the cell in S-phase. (wikipedia.org)
  • Cdt1 inhibits DNA synthesis by suppressing CMG helicase progression at replication forks through the MCM-binding domain of Cdt1, and DNA synthesis commences once Cdt1 is degraded. (biorxiv.org)
  • A high-resolution protein architecture of the budding yeast genome. (nature.com)
  • In these cases, it is indicated that the affected organism presents genome instability (also genetic instability, or even chromosomic instability). (wikipedia.org)
  • Rare fragile sites can lead to genetic disease such as fragile X mental retardation syndrome, myotonic dystrophy, Friedrich's ataxia, and Huntington's disease, most of which are caused by expansion of repeats at the DNA, RNA, or protein level. (wikipedia.org)
  • One focus of this research is on cancer genomes, with the goal of understanding the sources of genetic instability. (ucsc.edu)
  • Breaks in DNA strands also occur naturally when chromosomes exchange genetic material during cell division. (medlineplus.gov)
  • Efficient repair of damaged DNA strands helps maintain the stability of the cell's genetic information. (medlineplus.gov)
  • Misregulation of RAD51 regulators leads to genome instability and cancer. (nih.gov)
  • results from their study show the importance of the RAD51 nucleoprotein filament conformation for stimulating DNA pairing by BLM . (medscape.com)
  • Genome instability is a hallmark of cancer, and gives tumor cells many selective advantages, accelerating the evolutionary processes which allow cancers to thrive. (biomedcentral.com)
  • The Haussler lab's cancer genomics program provides a complete pipeline for analysis of DNA and RNA sequences from tumor samples. (ucsc.edu)
  • The authors measured the DNA copy numbers to identify structural variations in the tumor cells. (harvard.edu)
  • Localization and sequence analysis of yeast origins of DNA replication. (nature.com)
  • The others are the site-specific TFs or the DNA sequence-specific binding proteins. (intechopen.com)
  • Parkhill J , Wren BW , Thomson NR , Titball RW , Holden MT , Prentice MB , Genome sequence of Yersinia pestis , the causative agent of plague. (cdc.gov)
  • Single-stranded annealing provides end joining between interspersed nucleotide repeats within the genome leading to one copy of the repeat and the intervening sequence being deleted in the process. (news-medical.net)
  • Second, we highlight the importance and potential of complete or 100% genome sequencing, i.e., the ability to sequence highly repetitive non-coding sequences beyond the reach of current NGS technologies. (frontiersin.org)
  • The proper copying and repair of DNA to maintain the correct sequence and structure of genomes is critical to the proper function of cells, and repair and replication is frequently disrupted in cancers and targeted by cancer treatments. (birmingham.ac.uk)
  • The recently acquired genome sequence of globe artichoke (Cynara cardunculus var. (researchgate.net)
  • The same search parameters were applied to reveal the SSR content of 14 other plant species for which genome sequence is available. (researchgate.net)
  • The program encompasses basic as well as patient-oriented (translational) research and includes the use of various model systems (such as yeast, worms, mice and mammalian cell culture), and state-of-the-art technologies (e.g. next generation sequence technologies, genome- and proteome-wide screens). (lumc.nl)
  • There are hotspots in the genome where DNA sequences are prone to gaps and breaks after inhibition of DNA synthesis such as in the aforementioned checkpoint arrest. (wikipedia.org)
  • Xu, W., Aparicio, J. G., Aparicio, O. M. & Tavaré, S. Genome-wide mapping of ORC and Mcm2p binding sites on tiling arrays and identification of essential ARS consensus sequences in S. cerevisiae . (nature.com)
  • Wiechmann I , Harbeck M , Grupe G . Yersinia pestis DNA sequences in late medieval skeletal finds, Bavaria. (cdc.gov)
  • In it, we described the detection of several Yersinia pestis -specific plasmid pPCP1 DNA sequences in skeletal remains from a late medieval mass burial in Bavaria, Germany. (cdc.gov)
  • Homologous recombination involves the exchange of nucleotide sequences to repair damaged bases on both strands of DNA through the utilization of a sister chromatid. (news-medical.net)
  • Classical nonhomologous end joining connects the break ends without a homologous template through the use of short DNA sequences called microhomologies. (news-medical.net)
  • Chromosomes in which fragments of exogenous DNA ranging in length up to several hundred kilobase pairs have been cloned into yeast through ligation to vector sequences. (harvard.edu)
  • In conclution, DNA amplification is a rapid, reliable and accurate method with a high degree of sensitivity and specificity for the detection of Mycobacterium tuberculosis DNA sequences and it can replace the conventional culture method in the diagnosis of extra pulmonary tuberculosis and tuberculosis meningitis except in the situation when antibiotic sensitivity results are required. (who.int)
  • Each protein or enzyme in the replisome must perform its function well to result in a perfect copy of DNA. (wikipedia.org)
  • They also further defined subtype 1 as representing cell proliferation-related processes (cell cycle and DNA replication RNA processing, translation, and protein degradation). (genomeweb.com)
  • This protein plays a pivotal role in DNA recombination and repair. (medscape.com)
  • Additionally, the ATM protein assists cells in recognizing damaged or broken DNA strands. (medlineplus.gov)
  • The ATM protein coordinates DNA repair by activating enzymes that fix the broken strands. (medlineplus.gov)
  • Because of its central role in cell division and DNA repair, the ATM protein is of great interest in cancer research. (medlineplus.gov)
  • These DNA lesions can cause replication fork stalling and lead to DNA double-strand breaks that are canonically repaired by the homologous recombination (HR) pathway. (nih.gov)
  • Using genome-wide CRISPR /Cas9 screens we have also established, in collaboration with the Durocher laboratory (University of Toronto), that deficiency for RNase H2 leads to synthetic lethality with PARP inhibitors, small molecule inhibitors with proven efficacy in targeting homologous recombination (HR)-deficient cancers. (cam.ac.uk)
  • [ 7 , 8 ] Sister chromatid exchanges are considered a sensitive indicator for cell genome instability, as they are thought to be the outcome of DNA double-strand breaks resulting from homologous recombination repair. (medscape.com)
  • No amplification was obtained in DNA-free PCR mix and 5 Y. enterocolitica -negative control isolates, whereas sequencing yielded a 3-T homopolymeric tract in all 12 Y. pestis isolates. (cdc.gov)
  • As the integration of NGS in the study and treatment of cancer continues to mature, we believe that the field of cancer genomics will need to move toward more complete 100% genome sequencing. (frontiersin.org)
  • The rapid development of DNA sequencing technologies has driven a revolution in our understanding of this highly complex and diverse group of diseases ( Devita and Rosenberg, 2012 ). (frontiersin.org)
  • By selecting organisms resistant to the novel inhibitors and sequencing their genomes, we identified a new therapeutic target, the class Ia ribonucleotide reductase (RNR). (elifesciences.org)
  • The Srs2 helicase unwinds DNA hairpins, facilitates replication, and prevents repeat instability and fragility. (tufts.edu)
  • Predicted to contribute to single-stranded DNA helicase activity. (nih.gov)
  • Thus, instead of separating licensing from firing to prevent re-replication in early S phase, cells separate licensing from DNA synthesis through Cdt1-mediated inhibition of CMG helicase after firing. (biorxiv.org)
  • Crystal structure of the Bloom syndrome helicase BLM in complex with DNA (PDB ID: 4CGZ). (medscape.com)
  • The process of genome instability often leads to a situation of aneuploidy, in which the cells present a chromosomic number that is either higher or lower than the normal complement for the species. (wikipedia.org)
  • The cells that arrested were able to survive due to the increased time in S/G2 phase allowing for DNA repair enzymes to function fully. (wikipedia.org)
  • Here, using quantitative microscopy, we show that Cdt1 inhibits DNA synthesis during an overlap period when cells fire origins while Cdt1 is still present. (biorxiv.org)
  • The DNA within the nuclei of our cells carries the information to generate the machinery of the cell, the cell itself, our tissues and then the whole human. (birmingham.ac.uk)
  • For example, the chromosome that normally has sections in order as A-B-C-D might instead have sections A-B-C-C-D (a duplication of "C") or A-B-D (a deletion of "C"). The authors theorized that cigarette smoking serves as an environmental stressor on the cells and contributes to genome instability, generating DNA changes in certain chromosomes. (harvard.edu)
  • Genome-wide methylated CpG island profiles of melanoma cells reveal a melanoma coregulation network. (kgi.edu)
  • Our results propose a mechanism for progerin-induced genome instability and accelerated replicative senescence in HGPS. (nih.gov)
  • A new study led by Harvard School of Public Health (HSPH) researchers used a genome-wide analysis to assess abnormalities in the DNA structure of 264 nonsmallcell-lung cancer (NSCLC) tumors from Boston patients and compared the findings to the average number of cigarette packs smoked per year by the patients. (harvard.edu)
  • While scientists have known that DNA alterations occurred in lung cancer tumors, "this carefully assembled molecular epidemiology study had the additional exposure information to make the connection [to smoking as the cause]," Christiani said. (harvard.edu)
  • Methylation of guanine bases produces a change in the structure of DNA by forming a product that is complimentary to thymine rather than cytosine. (news-medical.net)
  • Required for genome wide de novo methylation and is essential for development. (lu.se)
  • RNA-DNA hybrids form through DNA polymerase errors, Okazaki fragment primers, and as R-loops during transcription. (northwestern.edu)
  • The enzymes remove the damaged base forming an AP site which is repaired by AP endonuclease before the nucleotide gap in the DNA strand is filled by DNA polymerase. (news-medical.net)
  • The third excision mechanism is called mismatch repair and occurs when mismatched bases are incorporated into the DNA strand during replication and are not removed by proofreading DNA polymerase. (news-medical.net)
  • Genome instability does occur in bacteria. (wikipedia.org)
  • Within the genome, many processes occur almost simultaneously so that the regulation of possibly chaotic access is tightly controlled. (birmingham.ac.uk)
  • Recent studies from our lab and others identified novel additional roles of these proteins in non-canonical repair during DNA lesion recognition, response to replication stress, and transcription coupled repair of replication structures containing R-loops. (nih.gov)
  • The course provides an overview of the methods used in laboratories of clinical genetics including prenatal cytogenetics, postnatal cytogenetics, cytogenetics in oncology, molecular cytogenetics and modern DNA and RNA diagnostic methods. (muni.cz)
  • Ribonucleotides are the most abundant non-canonical nucleotides in the mammalian genome, with over 1 million DNA -embedded ribonucleotides per replicating cell, posing a significant challenge to genome stability. (cam.ac.uk)
  • Ribonucleotides incorporated during DNA replication are normally removed by Ribonuclease (RNase) H2, a developmentally essential enzyme that initiates error-free ribonucleotide excision repair (RER). (cam.ac.uk)
  • Introduction: The genome is constantly exposed to numerous stressors, which induce DNA lesions, including double-stranded DNA breaks (DSBs). (bvsalud.org)
  • Nieduszynski, C. A., Knox, Y. & Donaldson, A. D. Genome-wide identification of replication origins in yeast by comparative genomics. (nature.com)
  • Here, using genome-scale biochemical reconstitution with approximately 300 replication origins, we screened 17 purified chromatin factors from budding yeast and found that the ORC established nucleosome depletion over replication origins and flanking nucleosome arrays by orchestrating the chromatin remodellers INO80, ISW1a, ISW2 and Chd1. (nature.com)
  • Design of a synthetic yeast genome. (harvard.edu)
  • PROJECT SUMMARY/ABSTRACT Alkylating agents in our environment from tobacco, pesticides, and produced during drinking water purification cause DNA lesions. (nih.gov)
  • It is a multifunctional nuclease and plays crucial roles in DNA mismatch repair (MMR), double-stranded break repair (DSBR), nucleotide excision repair (NER), immunoglobulin maturation, and telomere maintenance [ 18 - 21 ]. (hindawi.com)
  • DNA encodes the cell genome and is therefore a permanent copy of a structure necessary for the correct functioning of a cell. (news-medical.net)
  • While each DNA blueprint, or gene, encodes for a different machine or structure, the genome, the collection of DNA wrapped up inside the nucleus, is much more active than a quiet library of neatly stacked blue-prints. (birmingham.ac.uk)
  • Berbenetz, N. M., Nislow, C. & Brown, G. W. Diversity of eukaryotic DNA replication origins revealed by genome-wide analysis of chromatin structure. (nature.com)
  • 2022. Ribonucleotide incorporation by eukaryotic B-family replicases and its implications for genome stability. (nih.gov)
  • 2022. Ribonucleotide incorporation by eukaryotic B-family DNA replicases and its consequences. (nih.gov)
  • A fundamental concept in eukaryotic DNA replication is the temporal separation of G1 origin licensing from S phase origin firing. (biorxiv.org)
  • RNase H and multiple RNA biogenesis factors cooperate to prevent RNA:DNA hybrids from generating genome instability. (harvard.edu)
  • Specialized helicases play an important role in unwinding DNA structures to maintain genome stability. (tufts.edu)
  • In the cell cycle, DNA is usually most vulnerable during replication. (wikipedia.org)
  • The absence of either ATM or ATR in ctc1 and stn1 mutants significantly enhances developmental and genome instability while reducing stem cell death. (nih.gov)
  • Generally, problems with DNA replication or repair during periods of rapid cell division can cause instability in the genome, which results in cellular stress and inflammation. (nih.gov)
  • 3) How does the cell protect genome stability in response to DNA replication stress? (mdanderson.org)
  • In multicellular organisms genome instability is central to carcinogenesis, and in humans it is also a factor in some neurodegenerative diseases such as amyotrophic lateral sclerosis or the neuromuscular disease myotonic dystrophy. (wikipedia.org)
  • Approximately 15% of patients follow a primary progressive or progressive relapsing course from disease onset, usually characterized by symptoms of progressive myelopathy (gait instability, spasticity, bladder symptoms) and cognitive impairment. (medscape.com)
  • The non-defective strand is used as a template with the damaged DNA on the other strand removed and replaced by the synthesis of new nucleotides. (news-medical.net)
  • Re-replication and genome instability ensue if licensing occurs after DNA synthesis has started. (biorxiv.org)