• When DNA polymerase encounters an abasic site, DNA replication is usually blocked, which may itself lead to a single-stranded or double-stranded break in the DNA helix. (wikipedia.org)
  • Has DNA lyase activity and introduces double-stranded breaks at abasic sites. (thermofisher.com)
  • Cleaves both single-stranded DNA and double-stranded DNA at abasic sites, with the greatest activity towards double-stranded DNA with two abasic sites. (thermofisher.com)
  • Lyn, a tyrosine kinase that is activated by double-stranded DNA-damaging agents, is involved in various signaling pathways, such as proliferation, apoptosis, and DNA repair. (bmbreports.org)
  • In this process, a DNA glycosylase recognizes a damaged base and cleaves the N-glycosidic bond to release the base, leaving an AP site. (wikipedia.org)
  • A variety of glycosylases that recognize different types of damage exist, including oxidized or methylated bases, or uracil in DNA. (wikipedia.org)
  • Enzymes, namely DNA glycosylases, also commonly create AP sites, as part of the base excision repair pathway. (wikipedia.org)
  • DNA glycosylases first create abasic sites by recognizing and removing modified bases. (wikipedia.org)
  • Here, we report two in vitro models of APPXLs synthesized by cross-linking of DNA glycosylases Fpg and OGG1 to DNA followed by trypsinolysis. (bvsalud.org)
  • This results in an acceleration of the overall repair process of oxidized purines to yield an APE1-cleaved abasic site, which can be used as a substrate by DNA polymerase beta. (nih.gov)
  • Here, we provide evidence that DNA polymerase ß (POLB) of base excision repair (BER) pathway plays a critical role in the survival and thiopurine resistance of MMR-deficient ALL cells. (bvsalud.org)
  • DNA Polymerase ß (Polß) is a key enzyme in base excision repair (BER), which is very important in maintaining the stability and integrity of the genome. (bvsalud.org)
  • In a given mammalian cell, 5000-10,000 apurinic sites are estimated to form per day. (wikipedia.org)
  • XRCC1 participates in DNA single strand break and base excision repair (BER) to preserve genetic stability in mammalian cells. (nih.gov)
  • In these aggressive resistant ALL cells, POLB depletion and its inhibitor oleanolic acid (OA) treatment result in synthetic lethality with MMR deficiency through increased cellular apurinic/apyrimidinic (AP) sites, DNA strand breaks and apoptosis. (bvsalud.org)
  • More importantly, the results unveil a highly coordinated mechanism by which XRCC1, through its multiple protein-protein interactions, extends its orchestrating role from the base excision step to the resealing of the repaired DNA strand. (nih.gov)
  • The E. coli alkB protein is part of the adaptive response mechanism of DNA alkylation damage repair. (thermofisher.com)
  • Ribosomal protein S3 (RpS3) is involved in protein biosynthesis as a component of the ribosome complex and possesses endonuclease activity to repair damaged DNA. (bmbreports.org)
  • AP sites and their derivatives readily trap DNA-bound proteins, resulting in DNA-protein cross-links. (bvsalud.org)
  • In E. coli, when the enzyme manages to bypass the abasic site, an adenine is preferentially incorporated into the new strand. (wikipedia.org)
  • XRCC1 stimulates the formation of the hOGG1 Schiff-base DNA intermediate without interfering with the endonuclease activity of APE1, the second enzyme in the pathway. (nih.gov)
  • However, the repair mechanism of thiopurine-induced DNA damage in the absence of MMR remains unclear. (bvsalud.org)
  • Emerging evidence suggests that aberrant DNA repair is an underlying mechanism of lupus development. (bvsalud.org)
  • Both mechanisms form a single-strand break, which is then repaired by either short-patch or long-patch base excision repair. (wikipedia.org)
  • Dioxygenase that repairs alkylated single-stranded DNA and RNA containing 3-methylcytosine by oxidative demethylation. (thermofisher.com)
  • AP sites are an important feature of the base excision repair pathway. (wikipedia.org)
  • Our data suggest that APPXLs produced by proteolysis of AP site-trapped proteins may be removed by the BER pathway, at least in bacterial and yeast cells. (bvsalud.org)
  • Further results showed that Polß deficiency caused more DNA damage accumulation in cells and triggered the leakage of damaged DNA into the cytoplasm, which activated the STING/IRF3 pathway, promoted phosphorylated IRF3 translocating into the nucleus and enhanced the expression of type I interferon and proinflammatory cytokines. (bvsalud.org)
  • Taken together, our findings provide mechanistic insight into the role of Polß in cancers by linking DNA repair and the inflammatory STING pathway. (bvsalud.org)
  • Exposure to a nucleophile can cause a β-elimination reaction, wherein the 3' phosphoester bond is broken, causing a single-stranded break. (wikipedia.org)
  • This reaction can be catalyzed by AP lyase. (wikipedia.org)
  • AP sites can be formed by spontaneous depurination, but also occur as intermediates in base excision repair. (wikipedia.org)
  • Apurinic/apyrimidinic (AP) sites are abundant DNA lesions arising from spontaneous hydrolysis of the N-glycosidic bond and as base excision repair (BER) intermediates. (bvsalud.org)
  • The single-stranded breaks occurring due to β-elimination require repair by DNA Ligase in order to avoid mutation. (wikipedia.org)
  • Here, we report that XRCC1 interacts physically and functionally with hOGG1, the human DNA glycosylase that initiates the repair by BER of the mutagenic oxidized base 8-oxoguanine. (nih.gov)
  • The glycosidic linkages in DNA can be broken via acid-catalyzed hydrolysis. (wikipedia.org)
  • AP sites in living cells can cause various and severe consequences, including cell death. (wikipedia.org)
  • This interaction leads to a 2- to 3-fold stimulation of the DNA glycosylase activity of hOGG1. (nih.gov)
  • Our findings suggest BER and POLB's roles in the process of repairing thiopurine-induced DNA damage in MMR-deficient ALL cells, and implicate their potentials as therapeutic targets against aggressive ALL progression. (bvsalud.org)
  • Alkylation, deamination, and oxidation of individual bases can all lead to the weakening of the glycosyl bond, so exposure to agents that cause those modifications can encourage AP site formation. (wikipedia.org)
  • Ionizing radiation can also lead to AP site formation. (wikipedia.org)
  • Apyrimidinic sites form at a rate roughly 20 times slower, with estimates at around 500 formation events per day, per cell. (wikipedia.org)
  • The AP site can then be cleaved by an AP endonuclease, leaving 3'-hydroxyl and deoxyribose-5-phosphate termini (see DNA structure). (wikipedia.org)
  • An example of an endonuclease that will act on an AP sites is Endo IV. (neb.com)
  • To cleave the DNA backbone, another enzyme such as Endonuclease VIII is required. (neb.com)
  • However, apyrimidinic/apurinic (AP) endonuclease-deficient cells (xth nfo strain) were very sensitive to killing by NO(.), which indicates that normal processing of abasic sites is critical for defense against NO(.). In addition, recA mutant cells were exquisitely sensitive to NO(.)-induced killing. (nih.gov)
  • We determined whether H3K56Ac plays a role in regulating AP site incision by AP endonuclease 1 (APE1), an early step in BER. (nih.gov)
  • The structure of the major human apurinic/ apyrimidinic endonuclease (HAP1) has been solved at 2.2 A resolution. (nih.gov)
  • Structural comparison of AP endonucleases from the exonuclease III family reveals new amino acid residues in human AP endonuclease 1 that are involved in incision of damaged DNA. (nih.gov)
  • Excision of the lesion is achieved by strand displacement synthesis in the presence of flap endonuclease during which C2-AP and the 3'-adjacent nucleotide are replaced. (tamu.edu)
  • The iron-sulphur cluster loop (FCL) is also found in DNA-(apurinic or apyrimidinic site) lyase, a subfamily of endonuclease III. (embl-heidelberg.de)
  • The enzyme has both apurinic and apyrimidinic endonuclease activity and a DNA N-glycosylase activity. (embl-heidelberg.de)
  • Endonuclease V (EndoV) in E. coli is active upon DNA exposed to UV light, OsO4, acids, or X-rays [ 10 ]. (biomedcentral.com)
  • This enzyme was later characterized as 3′-deoxyinosine endonuclease that incises the DNA at the second phosphodiester bond 3′ to the dI lesion, leaving 3′-OH and 5′-P termini [ 13 ]. (biomedcentral.com)
  • In alternative fashion, bifunctional glycosylase-lyases can cleave the AP site, leaving a 5' phosphate adjacent to a 3' α,β-unsaturated aldehyde. (wikipedia.org)
  • Fpg is a bifunctional DNA glycosylase with DNA N-glycosylase and AP lyase activities. (neb.com)
  • N-glycosylase activity releases damaged purines, including 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) and 8-oxo-7,8-dihydroguanine (8-oxoG), generating an AP site. (neb.com)
  • Escherichia coli MutY is an adenine glycosylase involved in base excision repair that recognizes OG:A (where OG = 7, 8-dihydro-8-oxo-2'-deoxyguanosine) and G:A mismatches in DNA. (embl-heidelberg.de)
  • The excision of base damage is initiated by a specific DNA glycosylase: Hypoxanthine is bound and excised efficiently by human N -methylpurine-DNA glycosylase (MPG, also known as AAG, ANPG, APNG, or MDG) [ 6 ]. (biomedcentral.com)
  • In Escherichia coli , early studies indicated that the DNA glycosylase encoded by alkA gene could recognize and release hypoxanthine residues from DNA [ 1 ]. (biomedcentral.com)
  • The base excision repair (BER) pathway corrects most endogenous base lesions, including alkylation, oxidation and deamination, apurinic/apyrimidinic (AP) sites as well as single-strand breaks. (springer.com)
  • Alkylation, deamination, and oxidation of individual bases can all lead to the weakening of the glycosyl bond, so exposure to agents that cause those modifications can encourage AP site formation. (wikipedia.org)
  • Deoxyinosine (hypoxanthine deoxyribonucleotide, dI) in DNA can arise from spontaneous deamination of deoxyadenosine residue, and is also induced by ROS produced from normal aerobic respiration. (biomedcentral.com)
  • Deoxyinosine derived from deamination of deoxyadenosine in DNA is potentially mutagenic since it prefers to pair with dCTP during replication, yielding A:T to G:C transition mutations at sites of adenine deamination [ 5 ]. (biomedcentral.com)
  • Structure-dependent endos, which include wide variety of DNA repair enzymes, require a specific DNA structure or damaged base for activity, and will cleave an internal phosphodiester bond at that structure or damaged base. (neb.com)
  • After its recruitment by Ku, LigD would form a complex with the DNA, most probably implying the interaction of Lys331 with one of the phosphates of the phosphodiester bond between the AP site and the next 3' nucleotide ( b ). (uam.es)
  • Various types of DNA damage are repaired through multiple repair pathways, such as base excision, nucleotide excision, homologous recombination and nonhomologous end joining. (springer.com)
  • There are six known systems of DNA repair: pathway of direct reversion of damage, base excision repair (BER), nucleotide-excision repair (NER), mismatch repair (MMR), homologous recombination (HR) and nonhomologous DNA end joining (NHEJ). (springer.com)
  • It catalyzes the cleavage of DNA phosphodiester backbone at AP sites via hydrolysis, leaving a 1 nucleotide gap with 3´-hydroxyl and 5´-deoxyribose phosphate (dRP) termini. (neb.com)
  • The oxidized abasic lesion is also a substrate for the bacterial UvrABC nucleotide excision repair system. (tamu.edu)
  • Acting in concert with polymerization, those activities endow bacterial PolXs with the faculty to perform abasic site (AP) recognition, incision and further restoration (repair) of the original non-damaged nucleotide, as well as processing of the 3'-damaged ends that can arise after the exposition of the DNA to genotoxic agents. (uam.es)
  • The templating nucleotide opposite the AP site directs the binding of the complementary ribonucleotide, forming a Watson-Crick base pair at the polymerization site of the PolDom ( c ). (uam.es)
  • PolDom mediates further synapsis between the 3' overhanging strands from opposing breaks catalyzing the in trans addition of the nucleotide to the 3'-end of the incoming primer ( e ). (uam.es)
  • These loop regions apparently act in DNA abasic site (AP) recognition and cleavage since DNase I, which lacks these loops, correspondingly lacks AP site specificity. (nih.gov)
  • Coupling of AP sites cleavage to the end-joining reaction by the B. subtilis LigD. (uam.es)
  • Our in vitro studies of acetylated, well-positioned nucleosome core particles (H3K56Ac-601-NCPs) demonstrate APE1 strand incision is enhanced compared with that of unacetylated WT-601-NCPs. (nih.gov)
  • In E. coli, when the enzyme manages to bypass the abasic site, an adenine is preferentially incorporated into the new strand. (wikipedia.org)
  • The AP endonucleases cleave an AP site to yield a 3′ hydroxyl adjacent to a 5′ deoxyribosephosphate (dRP). (springer.com)
  • Endonucleases cleave DNA internally, and do not require free DNA ends for activity. (neb.com)
  • Structure-independent endos randomly cleave internal phosphodiester bonds, and are named such because they do not require a specific DNA structure for activity. (neb.com)
  • These are processive enzymes, and once activity has been initiated, the endo will continue to cleave DNA. (neb.com)
  • The single-stranded breaks occurring due to β-elimination require repair by DNA Ligase in order to avoid mutation. (wikipedia.org)
  • We have recently characterized the additional presence of an unexpected 5'-2-deoxyribose-5-phosphate (dRP) lyase activity in the ligase domain (LigDom) of the LigD from B. subtilis and P.aeruginosa . (uam.es)
  • This activity coordinates with the polymerization and ligase activities to allow efficient repairing of an AP site-containing DNA in an in vitro reconstituted Base Excision Repair (BER) reaction. (uam.es)
  • One consequence of these double-strand ends is that NO(.) induces homologous recombination at a genetically engineered substrate. (nih.gov)
  • It appears from literature that human cytomegalovirus enhances DNA repair capacity in host cells, without producing detectable lesions in cellular DNA or inhibiting DNA synthesis (Nishiyama and Rapp 1981 ). (springer.com)
  • Many bacterial members are provided with a nonhomologous end joining system (NHEJ) responsible for repairing double strand breaks (DSB), the most hazardous DNA lesions as they are lethal to dividing cells if they are not repaired in a timely fashion. (uam.es)
  • AP sites are the most common genomic DNA lesions frequently associated with DSBs. (uam.es)
  • In biochemistry and molecular genetics, an AP site (apurinic/apyrimidinic site), also known as an abasic site, is a location in DNA (also in RNA but much less likely) that has neither a purine nor a pyrimidine base, either spontaneously or due to DNA damage. (wikipedia.org)
  • Apurinic or apyrimidinic sites, also known AP or abasic sites are common and occur spontaneously in DNA when a base is lost. (neb.com)
  • The HAP1 structure furthermore suggests a mechanism for AP site binding which involves the recognition of the deoxyribose moiety in an extrahelical conformation, rather than a 'flipped-out' base opposite the AP site. (nih.gov)
  • Aside from DNA repair enzymes, there are also structure-specific endonucleases that act on DNA secondary structure. (neb.com)
  • The properties of the R194A, K196A, and K198A enzymes were also compared to the properties of mutated enzymes in which lysine residues near the active site pocket were replaced with alanine or glycine. (embl-heidelberg.de)
  • H3K56 acetylation (Ac) is implicated in chromatin landscape regulation, impacting genomic stability, yet the effect of H3K56Ac on DNA base excision repair (BER) remains unclear. (nih.gov)
  • Our main objective is to get insights on the molecular mechanisms responsible for maintaining genome stability in bacteria, by functional analysis of the enzymatic features of purified repair proteins from model organisms as the gram positive bacterium Bacillus subtilis whose vegetative cells and spores have to handle DNA damage induced by extreme environmental conditions, and the gram negative Pseudomonas aeruginosa . (uam.es)
  • AP sites can be formed by spontaneous depurination, but also occur as intermediates in base excision repair. (wikipedia.org)
  • Once the preternary-precatalytic complex is stabilized, the protein incises at the AP site, releasing the cleaved strand and giving rise to a new 5'-P end ( d ). (uam.es)
  • AP sites form when deoxyribose is cleaved from its nitrogenous base, breaking the glycosidic linkage between the two. (wikipedia.org)
  • Hydroxyl radicals can attack the glycosidic linkages, directly creating an AP site, or make the glycosyl bond less favorable by linking to the base or the deoxyribose ring. (wikipedia.org)
  • Both mechanisms form a single-strand break, which is then repaired by either short-patch or long-patch base excision repair. (wikipedia.org)
  • AP site formation can also be caused by various base-modifying chemicals. (wikipedia.org)
  • These data suggest that the redundant nature of DNA repair systems provides a means for removing a lesion that resists excision by short patch base excision repair. (tamu.edu)
  • Structure-independent endos are primarily used to clean-up DNA contamination. (neb.com)
  • After the breakage, the DNA end is threaded through the open ring-like structure of the Ku dimer ( a ). (uam.es)
  • Herpesvirus infections, such as those induced by human cytomegalovirus (HCMV), induce specific DNA damages. (springer.com)
  • The control aspects of the five DNA repair mechanisms in virus-infected cells have not been well characterized. (springer.com)
  • AP sites in living cells can cause various and severe consequences, including cell death. (wikipedia.org)
  • Both SOS-deficient (lexA3) and Holliday junction resolvase-deficient (ruvC) cells were very sensitive to NO(.), indicating that both SOS and recombinational repair play important roles in defense against NO(.). Furthermore, strains specifically lacking double-strand end repair (recBCD strains) were very sensitive to NO(.), which suggests that NO(.) exposure leads to the formation of double-strand ends. (nih.gov)
  • 8-oxoguanine, more commonly known as 8-oxoG, is a common DNA error that results from oxidizing guanine. (neb.com)
  • This process is enhanced by ROS from exposure of DNA to ionizing radiation, UV light, nitrous acid, or heat. (biomedcentral.com)
  • The FCL is located adjacent to the proposed active site pocket and has been suggested to be part of the DNA binding surface of MutY (Y. Guan et al. (embl-heidelberg.de)
  • The viruses that induce cellular DNA damage include members of the herpesvirus group, adenovirus, mumps-virus, measles-virus, rubella-virus, poliovirus and papilloma-virus (Fortunato et al. (springer.com)
  • It is known that HCMV can act as mutagen inducing various DNA damage (AbuBakar et al. (springer.com)
  • Those experimental studies focused on repairs of exogenously introduced damage in cellular DNA in the context of single viral protein expression (Becker et al. (springer.com)
  • The location of the AP site proximal to the 5'-end could promote the partial melting of the 5'-end making the AP site accessible. (uam.es)
  • This report reviews results from studies, assaying a DNA repair system in HCMV infection. (springer.com)
  • In this review, considerations and results of the experiments are presented, supporting the thesis on the important role of DNA repair systems in HCMV- infected cell. (springer.com)