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  • protein
  • We show that the base excision repair protein apurinic/apyrimidinic endonuclease (APE) 2 protects activated B cells from oxidative damage in vitro. (jimmunol.org)
  • We studied the expression of human apurinic/apyrimidinic endonuclease (APE1), a key multifunctional protein involved in DNA base excision repair in RB. (bmj.com)
  • To avoid excessive DNA probing by the low specificity of the protein, the steady-state level in the nucleus is controlled by nucleus-cytoplasm shuttling, allowing temporally higher concentrations of XPC in the nucleus under genotoxic stress conditions. (uva.nl)
  • The tissue and cellular distribution of the DNA repair protein O6-alkylguanine-DNA-alkyltransferase (ATase) is an important question in relation to the response of tumour and normal tissues to chemotherapeutic regimes employing alkylating agents such as methyltriazenes and nitrosoureas. (openrepository.com)
  • damage
  • GC B cells can "tolerate" DNA damage while rapidly proliferating because of partial suppression of the DNA damage response by BCL6. (jimmunol.org)
  • In this study, we develop a model to study the response of mouse GC B cells to endogenous DNA damage. (jimmunol.org)
  • These results describe a nonredundant role for APE2 in the protection of GC cells from AID-independent damage, and although GC cells uniquely tolerate DNA damage, we find that the DNA damage response can still regulate GC size through pathways that involve p53 and BCL6. (jimmunol.org)
  • To investigate how the nucleotide excision repair initiator XPC locates DNA damage in mammalian cell nuclei we analyzed the dynamics of GFP-tagged XPC. (uva.nl)
  • Photobleaching experiments showed that XPC constantly associates with and dissociates from chromatin in the absence of DNA damage. (uva.nl)
  • DNA-damaging agents retard the mobility of XPC, and UV damage has the most pronounced effect on the mobility of XPC-GFP. (uva.nl)
  • cell
  • DNA double-strand breaks are increased in the rapidly dividing GC centroblasts of APE2-deficient mice, which activate a p53-independent cell cycle checkpoint and a p53-dependent apoptotic response. (jimmunol.org)
  • mutations
  • Changes to the structure of DNA can cause mutations and genomic instability, leading to cancer. (news-medical.net)
  • Of the thousands of random changes created every day in the DNA of a human cell by heat, metabolic accidents, radiation of various sorts, and exposure to substances in the environment, only a few accumulate as mutations in the DNA sequence. (nih.gov)
  • Although DNA is a highly stable material, as required for the storage of genetic information, it is a complex organic molecule that is susceptible, even under normal cellular conditions, to spontaneous changes that would lead to mutations if left unrepaired ( Figure 5-46 ). (nih.gov)
  • The mutations would then be propagated throughout subsequent cell generations as the DNA is replicated. (nih.gov)
  • A byproduct of alcohol consumption causes mutations in the DNA of mouse blood stem cells, and some of the breaks are not repaired. (the-scientist.com)
  • Researchers develop a CRISPR-based technique that efficiently corrects point mutations without cleaving DNA. (the-scientist.com)
  • Daughter cells that inherit these wrong bases carry mutations from which the original DNA sequence is unrecoverable (except in the rare case of a back mutation, for example, through gene conversion). (wikipedia.org)
  • Such DNA damages can cause errors during DNA synthesis leading to mutations, some of which may give rise to cancer. (wikipedia.org)
  • Germ-line DNA repair mutations that increase the risk of cancer are listed in the Table. (wikipedia.org)
  • Since XRCC4 is the key protein that enables interaction of LigIV to damaged DNA and therefore ligation of the ends, mutations in the XRCC4 gene were found to cause embryonic lethality in mice and developmental inhibition and immunodeficiency in humans. (wikipedia.org)
  • As with all DNA damage, DSBs can introduce new mutations that can ultimately lead to cancer. (wikipedia.org)
  • pathway
  • This DNA repair pathway protects cells against endogenous DNA lesion including single-strand breaks. (nih.gov)
  • The group and collaborators have reported many crystal structures of complexes of rat and human DNA polymerases beta with the two substrates (DNA and dNTP), and have solved the NMR structure of the enzyme's 8 kDa domain that contributes lyase activity in the base excision repair pathway. (nih.gov)
  • T, an indication that the redox pathway is DNA-mediated. (pnas.org)
  • DSBs that cannot rely on a newly copied sister chromosome generated by DNA replication to fill in the gap will go into the NHEJ pathway. (wikipedia.org)
  • For this circumstance, the NHEJ pathway provides a solution for repairing the break and is the main system used to repair DSBs in humans and multicellular eukaryotes. (wikipedia.org)
  • NER is a multi-step pathway that removes a variety of different DNA damages that alter normal base pairing, including both UV-induced damages and bulky chemical adducts. (wikipedia.org)
  • binds
  • Photolyase is a light-activated flavoenzyme that binds to pyrimidine dimers in DNA and repairs them in a reaction triggered by electron transfer from the photoexcited flavin cofactor to the dimer. (pnas.org)
  • XRCC4 binds to DNA, and to DNA ligase IV (LIG4) to form the LIG4-XRCC4 complex [ PMID: 11029705 ]. (ebi.ac.uk)
  • MutS forms a dimer (MutS2) that recognises the mismatched base on the daughter strand and binds the mutated DNA. (wikipedia.org)
  • MutH binds at hemimethylated sites along the daughter DNA, but its action is latent, being activated only upon contact by a MutL dimer (MutL2), which binds the MutS-DNA complex and acts as a mediator between MutS2 and MutH, activating the latter. (wikipedia.org)
  • Rare fragile sites (RFSs) are classified into two sub-groups based on the compounds that elicit breakage: folate-sensitive groups (for examples, see ), and nonfolate-sensitive groups, which are induced by bromodeoxyuridine (BrdU) or distamycin A, an antibiotic that preferentially binds to AT-pairs of DNA. (wikipedia.org)
  • replication forks
  • The CGG and AT-rich repeats characteristic of RFSs can form hairpins and other non-B DNA structures that block replication forks and can result in breakage. (wikipedia.org)
  • CAF-1 mediates the first step in nucleosome formation by tetramerization and depositing newly synthesized histone H3/H4 onto DNA rapidly behind replication forks. (wikipedia.org)
  • organisms
  • For example, analysis of the genomes of bacteria and yeasts has revealed that several percent of the coding capacity of these organisms is devoted solely to DNA repair functions. (nih.gov)
  • Many DNA repair pathways and the genes that encode them-which we now know operate in a wide variety of organisms, including humans-were originally identified in bacteria by the isolation and characterization of mutants that displayed an increased mutation rate or an increased sensitivity to DNA-damaging agents. (nih.gov)
  • Sunburn in living organisms is caused by ultraviolet (UV) light from the sun damaging the DNA in the cells. (phys.org)
  • ligase
  • Requirement for XRCC4 and DNA ligase IV in alignment-based gap filling for nonhomologous DNA end joining in vitro. (ebi.ac.uk)
  • The second component involves the bridging of DNA to DNA Ligase IV (LigIV), by XRCC4, with the aid of Cernunos-XLF. (wikipedia.org)
  • It is suspected that, in eukaryotes, newly synthesized lagging-strand DNA transiently contains nicks (before being sealed by DNA ligase) and provides a signal that directs mismatch proofreading systems to the appropriate strand. (wikipedia.org)
  • Formation of XRCC4-XLF oligomers can be disrupted by interaction of the C-terminal domain of XRCC4 with the BRCT domain of DNA ligase IV. (wikipedia.org)
  • bases
  • 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)
  • Similarly, a spontaneous deamination of cytosine to uracil in DNA occurs at a rate of about 100 bases per cell per day ( Figure 5-47 ). (nih.gov)
  • DNA bases are also occasionally damaged by an encounter with reactive metabolites (including reactive forms of oxygen) or environmental chemicals. (nih.gov)
  • Likewise, ultraviolet radiation from the sun can produce a covalent linkage between two adjacent pyrimidine bases in DNA to form, for example, thymine dimers ( Figure 5-48 ). (nih.gov)
  • bulky adduct formation" (i.e., benzo[a]pyrene diol epoxide-dG adduct, aristolactam I-dA adduct) mismatch of bases, due to errors in DNA replication, in which the wrong DNA base is stitched into place in a newly forming DNA strand, or a DNA base is skipped over or mistakenly inserted. (wikipedia.org)
  • Examples of mismatched bases include a G/T or A/C pairing (see DNA repair). (wikipedia.org)
  • Mismatches are commonly due to tautomerization of bases during DNA replication. (wikipedia.org)
  • molecular
  • The journal publishes original observations on genetic, cellular, biochemical, structural and molecular aspects of DNA repair, mutagenesis, cell cycle regulation, apoptosis and other biological responses in cells exposed to genomic insult, as well as their relationship to human disease . (elsevier.com)
  • Understanding how the human body recognizes damaged DNA and initiates repair fascinates Michael Feig, professor of biochemistry and molecular biology at Michigan State University. (redorbit.com)
  • Only poly-ubiquitination on defined lysines, mostly on K48 and K29, is related to degradation by the proteasome (referred to as the "molecular kiss of death"), while other polyubiquitinations (e.g. on K63, K11, K6 and M1) and monoubiquitinations may regulate processes such as endocytic trafficking, inflammation, translation and DNA repair. (wikipedia.org)
  • Trichothiodystrophy view from the molecular basis of DNA repair transcription factor TF11H.www.oxfordjournals.org/content/18/R2/R224 Nakabayashi K, Amann D, Ren Y, et al. (wikipedia.org)
  • defects
  • It becomes possible to bend the DNA in places where there are defects. (redorbit.com)
  • Yet, as cells grow and change, DNA is vulnerable to defects, especially double strand breaks (DSBs). (nanowerk.com)
  • Inherited Syndromes with Defects in DNA Repair. (nih.gov)
  • DNA repair defects can cause an accelerated aging disease or an increased risk of cancer, or sometimes both. (wikipedia.org)
  • DNA repair defects are seen in nearly all of the diseases described as accelerated aging disease, in which various tissues, organs or systems of the human body age prematurely. (wikipedia.org)
  • Ataxia-telangiectasia Bloom syndrome Cockayne syndrome Fanconi anemia Progeria (Hutchinson-Gilford progeria syndrome) Rothmund-Thomson syndrome Trichothiodystrophy Werner syndrome Xeroderma pigmentosum Some examples of DNA repair defects causing progeroid syndromes in humans or mice are shown in Table 1. (wikipedia.org)
  • Homozygotes of both sex had abnormal eye sizes, narrow eye openings, skeletal defects (including scoliosis and fusion of vertebrae), and displayed an increase in DNA instability as shown by a micronucleus test. (wikipedia.org)
  • enzyme
  • In 1996, the group demonstrated that Pol β "knock-out" mouse fibroblast cell lines are deficient in DNA repair and in cellular protection against DNA damaging agents, thus establishing a cellular role for this enzyme. (nih.gov)
  • report that a nuclear function of Bcl2 appears to be inhibition of the DNA repair enzyme APE1, which mediates the repair of apurinic/apyrimidinic (also known as abasic) sites that occur thousands of times each day in a cell due to various environmental stresses. (sciencemag.org)
  • Combining a modified Cas9 enzyme with an unrelated one derived from the immune system of the sea lamprey, researchers demonstrate yet another way to edit a single DNA nucleotide. (the-scientist.com)
  • During the MMR process, which occurs in cells throughout the animal and plant kingdom, an enzyme repairs parts of DNA that have been copied incorrectly during cell replication. (wn.com)
  • mismatches
  • A wealth of experimental data has established that DNA CT is exquisitely sensitive to even subtle perturbations in the base pair π-stack, including single base mismatches ( 3 , 8 , 9 ). (pnas.org)
  • In a paper published in the Journal of Physical Chemistry B (April 26, 2013), Feig and his research team showed that the identification and initiation of repair depended on how the MutS protein bound with the base mismatches. (redorbit.com)
  • mutagenesis
  • DNA Repair and Mutagenesis is a college-level textbook about DNA repair and mutagenesis written by Errol Friedberg, Graham Walker, Wolfram Siede, Richard D. Wood, and Roger Schultz. (wikipedia.org)
  • In its second edition as of 2009, DNA Repair and Mutagenesis contains over 1,000 pages, 10,000 references and 700 illustrations and has been described as "the most comprehensive book available in [the] field. (wikipedia.org)
  • occurs
  • The therapeutic benefit of temozolomide depends on its ability to alkylate/methylate DNA, which most often occurs at the N-7 or O-6 positions of guanine residues. (wikipedia.org)
  • cellular
  • FANCD is essential for cellular repair after cancer therapy. (novusbio.com)
  • CAF-1 (chromatin assembly factor-1) is a complex, including Chaf1a (p150), Chaf1b (p60) and p50 subunits that assembles histone tetramers onto replicating DNA in vitro This complex is histone chaperone involved in creating cellular memory of somatic cell identity - cellular differentiation. (wikipedia.org)
  • radiation
  • Cyclobutane pyrimidine dimers are the major DNA photoproducts produced upon exposure to UV radiation. (pnas.org)
  • In another human disease, xeroderma pigmentosum (XP), the afflicted individuals have an extreme sensitivity to ultraviolet radiation because they are unable to repair certain DNA photoproducts. (nih.gov)
  • One of these include ionizing radiation, such as γ radiation and X-rays, which ionize the deoxyribose groups in the DNA backbone and can induce DSBs. (wikipedia.org)
  • The DNA repair function of SLX4 is involved in sensitivity to proton beam radiation. (wikipedia.org)
  • structural
  • Biochemical ( 16 ) and structural ( 17 , 18 ) evidence indicates that, upon photolyase binding, the pyrimidine dimer is flipped out of the DNA helix into a pocket accessible to the flavin cofactor. (pnas.org)
  • Nanowerk News ) Osaka University scientists, in collaboration with The University of Tokyo, describe the crystal structure of RNF168 bound to ubiquitin chains, a crucial interaction for DNA repair, to find a unique interaction ( Nature Communications , 'Structural insights into two distinct binding modules for Lys63-linked polyubiquitin chains in RNF168' ). (nanowerk.com)
  • meiosis
  • This reduced fertility appears to be due to germ cell attrition resulting from a combination of unrepaired DNA breaks during meiosis and defective synapsis of the X and Y chromosomes. (wikipedia.org)
  • processes
  • DNA repair refers to a collection of processes by which cells identify and correct damaged DNA. (novusbio.com)
  • Most such spontaneous changes in DNA are temporary because they are immediately corrected by a set of processes that are collectively called DNA repair . (nih.gov)
  • The phenomenon was commonly attributed to "unbalanced growth" wherein cells continued fundamental processes of RNA transcription, protein synthesis and metabolism in the absence of DNA replication. (wikipedia.org)
  • abasic
  • First the authors compared the abasic site repair activity in human lung cancer cell lines and found that there was an inverse correlation between the repair activity and the abundance of Bcl2. (sciencemag.org)
  • The interaction between Bcl2 and APE1 and the ability of Bcl2 to inhibit APE1 activity in vitro and abasic site repair in cultured cells required all four BH3 domains of Bcl2. (sciencemag.org)
  • synthesis
  • 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)
  • the group demonstrated that alteration of key amino acid side chains cripples Pol β so that it no longer catalyzes DNA synthesis efficiently and does not discriminate between correct and incorrect incoming nucleotides. (nih.gov)
  • During DNA synthesis the newly synthesised (daughter) strand will commonly include errors. (wikipedia.org)
  • defective
  • It probably has effects on many other cancers as well, because all the cancers are ultimately linked to defective DNA," he said. (redorbit.com)
  • occur
  • According to Matt Cowperthwaite, TACC's medical informatics programs coordinator, Feig's research is enormously important for advancing our understanding of how cells repair the mistakes that inevitably occur during DNA replication. (redorbit.com)
  • NHEJ
  • During NHEJ, very short stretches of complementary DNA, 1 bp or more at a time, are hybridized together, and the overhangs are removed. (wikipedia.org)
  • helix
  • When bound, the MutS2 dimer bends the DNA helix and shields approximately 20 base pairs. (wikipedia.org)
  • breaks
  • The instability of CFSs is proposed to stem from late replication: CFSs are likely to initiate proper replication but slow to complete it, introducing breaks from unreplicated regions of DNA. (wikipedia.org)
  • DNA breaks were observed during thymineless death, which could explain the killing. (wikipedia.org)
  • helicase
  • MutL recruits UvrD helicase (DNA Helicase II) to separate the two strands with a specific 3' to 5' polarity. (wikipedia.org)