• A variety of different DNA repair pathways have been reported that include direct reversal, base excision repair, nucleotide excision repair, photoreactivation, bypass, double-strand break repair pathway, and mismatch repair pathway. (systemsbiology.net)
  • Thymine dimers are excised in bacteria by UvrABC proteins in a process known as nucleotide excision repair (NER) as illustrated in Figure 29.29. (pharmacy180.com)
  • Nucleotide excision repair of pyrimidine dimers in E. coli DNA. (pharmacy180.com)
  • ii) Spore DNA damage correction during spore germination is dependent upon nucleotide excision repair, recombination repair, and the SP-specific SP lyase repair systems. (photobiology.com)
  • 2000). The nucleotide excision repair (NER), recombinational repair (Rec), and spore photoproduct (SP) lyase DNA repair pathways are major determinants of spore resistance to 254-nm UV-C radiation in the laboratory ( Fig. 1 ). (photobiology.com)
  • 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)
  • 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)
  • The investigations described in this thesis report two novel findings: (1) the identification of a new class of adenine specific single-stranded DNA glycosylases and (2) the first description of DNA repair activities in Plasmodium falciparum, the protozoan parasite that causes human malaria. (jefferson.edu)
  • 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)
  • These enzymes are primarily from bacteria, and have both DNA glycosylase activity EC 3.2.2. (wikipedia.org)
  • Additionally, it was found that the removal of adenine by a single-strand DNA glycosylase activity was the first step in the cleavage of DNA. (jefferson.edu)
  • This interaction leads to a 2- to 3-fold stimulation of the DNA glycosylase activity of hOGG1. (nih.gov)
  • Whereas several enzymes are required to complete the multistep repair process of damaged bases, apurinic-apyrimidic (AP) endonucleases play an essential role in enabling the repair process by recognizing intermediary abasic sites cleaving the phosphodiester backbone 5' to the abasic site. (ox.ac.uk)
  • 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)
  • XRCC1 participates in DNA single strand break and base excision repair (BER) to preserve genetic stability in mammalian cells. (nih.gov)
  • Bases are also altered or lost spontaneously from mammalian DNA at a rate of many thousands per cell per day. (pharmacy180.com)
  • Co-administration of both drugs synergistically decreased cell viability and clonogenicity, and synergistically induced cell apoptosis and DNA damage, while had no detectable toxicity to normal prostate epithelial cells. (biomedcentral.com)
  • 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)
  • 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)
  • The data presented support a model by which XRCC1 will pass on the DNA intermediate from hOGG1 to the endonuclease APE1. (nih.gov)
  • 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)
  • Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein contributing to genome stability via repair of DNA lesions via the base excision repair pathway. (cnr.it)
  • The two DNA-binding motifs (a zinc finger and the H2TH (helix-two-turns-helix) motifs) suggest that the oxidised base is flipped out from double-stranded DNA in the binding mode and excised by a catalytic mechanism similar to that of bifunctional base excision repair enzymes. (wikipedia.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)
  • Furthermore, the structural mechanism for AP-site cleavage is incomplete. (ox.ac.uk)
  • 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)
  • 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)
  • Sometimes replication errors escape the proofreading function during DNA synthesis, causing a mismatch of one to several bases. (pharmacy180.com)
  • In E. coli, mismatch repair (MMR) is mediated by a group of proteins known as the Mut proteins (Figure 29.28). (pharmacy180.com)
  • Methyl-directed mismatch repair in E. coli. (pharmacy180.com)
  • Mutation to the proteins involved in mismatch repair in humans is associated with hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome. (pharmacy180.com)
  • however, only about 5% of all colon cancer is the result of mutations in mismatch repair. (pharmacy180.com)
  • Mismatch repair (MMR) deficiency has been linked to thiopurine resistance and hypermutation in relapsed acute lymphoblastic leukemia (ALL). (bvsalud.org)
  • The N-terminal catalytic domain and the C-terminal zinc finger straddle the DNA with the long axis of the protein oriented roughly orthogonal to the helical axis of the DNA. (wikipedia.org)
  • Our studies revealed that the synergistic lethality of HDAC and PARP inhibitors resulted from promoting DNA damage and inhibiting HR DNA damage repair pathways, in particular targeting the UHRF1/BRCA1 protein complex. (biomedcentral.com)
  • The members of the DNA Repair Interest Group perform research in areas including DNA repair enzymology and fine structure, mutagenesis, gene and cell cycle regulation, protein structure, and human disease. (nih.gov)
  • AP sites and their derivatives readily trap DNA-bound proteins, resulting in DNA-protein cross-links. (bvsalud.org)
  • In molecular biology, the H2TH domain (helix-2turn-helix domain) is a DNA-binding domain found in DNA glycosylase/AP lyase enzymes, which are involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. (wikipedia.org)
  • XRCC1 participation in these pathways is mediated by its interactions with several of the acting enzymes. (nih.gov)
  • On the contrary, the stimulation in the appearance of the incision product seems to reflect the addition of the effects of XRCC1 on the two first enzymes of the pathway. (nih.gov)
  • Our data reveal subtle differences in AP-site recognition and kinetics between the human and bacterial enzymes that may reflect different evolutionary pressures. (ox.ac.uk)
  • As a major defense against environmental damage to cells DNA repair is present in all organisms examined including bacteria, yeast, drosophila, fish, amphibians, rodents and humans. (nih.gov)
  • Base excision repair (BER) is a highly conserved DNA repair pathway throughout all kingdoms from bacteria to humans. (ox.ac.uk)
  • Its AP (apurinic/apyrimidinic) lyase activity introduces nicks in the DNA strand, cleaving the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates. (wikipedia.org)
  • Catalysis of the cleavage of the C-O-P bond 3' to the apurinic or apyrimidinic site in DNA by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate. (systemsbiology.net)
  • Structural basis for the recognition and cleavage of abasic DNA in Neisseria meningitidis. (ox.ac.uk)
  • The damaging agents can be either chemicals (for example, nitrous acid, which can deaminate bases), or radiation (for example, non-ionizing ultraviolet light, which can fuse two pyrimidines adjacent to each other in the DNA, and high-energy ionizing radiation, which can cause double-strand breaks). (pharmacy180.com)
  • 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)
  • and AP lyase activity EC 4.2.99.18. (wikipedia.org)
  • EC 3.2.2.23) and cleaves both the 3'- and 5'-phosphodiester bonds of the resulting apurinic/apyrimidinic site (AP lyase activity;EC 4.2.99.18). (wikipedia.org)
  • Because the mitochondrial DNA of P. falciparum appeared to be the target of gelonin's cytotoxic activity and contained single-stranded regions, we investigated the activity of gelonin on single stranded DNA. (jefferson.edu)
  • After the removal of adenine, the DNA was then cleaved, possibly by an associated lyase activity. (jefferson.edu)
  • This activity was unique, as there is no other report of a DNA glycosylase/AP lyase that acts on single stranded DNA. (jefferson.edu)
  • Lawson and colleagues reported that based on 3 years of data captured by the Quarantine Activity and Reporting System (QARS), vaccine-preventable and tropical diseases are not major causes of death in international travelers Vemurafenib ic50 arriving in the United States. (micrornaarray.com)
  • 2009). Accumulation of SAH caused by inhibition of SAHH activity had been shown to increase the concentration ratio of SAH/SAM to inhibit SAM-dependent methyltransfer reactions and consequently lead to a global decrease in DNA methylation reactions (Tanaka et al. (micrornaarray.com)
  • These functions are important for maintaining cellular homeostasis and are regulated through several pathways. (bmbreports.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)
  • Most of the repair systems involve recognition of the damage (lesion) on the DNA, removal or excision of the damage, replacement or filling the gap left by excision using the sister strand as a template for DNA synthesis, and ligation. (pharmacy180.com)
  • Despite extensive study, there is no structure of a bacterial AP endonuclease bound to substrate DNA. (ox.ac.uk)
  • It appears that the cell-free lysate from P. falciparum possesses a complete pathway for the repair of uracil damage and AP sites. (jefferson.edu)
  • Fpg has a preference for oxidised purines, excising oxidised purine bases such as 7,8-dihydro-8-oxoguanine (8-oxoG). (wikipedia.org)
  • Discrimination is based on the degree of methylation. (pharmacy180.com)
  • This methylation is not done immediately after synthesis, so the newly synthesized DNA is hemimethylated (that is, the parental strand is methylated, but the daughter strand is not). (pharmacy180.com)
  • 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)
  • 10] If a returning traveler (who truly had severe malaria) presented to an emergency department 2 weeks after returning from travel, a diagnosis of renal failure might be made based on creatinine levels. (micrornaarray.com)
  • It is likely that this pathway utilized a flap endonuclease to process the single-stranded DNA that occurs during repair synthesis. (jefferson.edu)
  • Despite the elaborate proofreading system employed during DNA synthesis, errors (including incorrect base-pairing or insertion of one to a few extra nucleotides) can occur. (pharmacy180.com)
  • Note: Repair synthesis of DNA can occur outside of the S phase. (pharmacy180.com)
  • The process of restoring DNA after damage. (systemsbiology.net)
  • 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)
  • If an Invitrogen™ antibody doesn't perform as described on our website or datasheet,we'll replace the product at no cost to you, or provide you with a credit for a future purchase. (thermofisher.com)
  • Luckily, cells are remarkably efficient at repairing damage done to their DNA. (pharmacy180.com)
  • UV resistance of spores and vegetative cells of B. subtilis DNA repair mutants. (photobiology.com)
  • 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)
  • Taken together, the data support a model in which spore resistance to solar UV results from a complex interplay of structural, photochemical, and DNA repair processes. (photobiology.com)
  • 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)
  • The investigation reported in Chapter Three characterized the repair of uracil mismatches and apurinic/apyrimidinic (AP) sites in DNA by a total cell lysate from P. falciparum. (jefferson.edu)
  • If the damage is not repaired, a permanent change (mutation) is introduced that can result in any of a number of deleterious effects, including loss of control over the proliferation of the mutated cell, leading to cancer. (pharmacy180.com)
  • Both the native and recombinant forms of gelonin were found to cause the degradation of single stranded DNA. (jefferson.edu)
  • In addition, DNA is constantly being subjected to environmental insults that cause the alteration or removal of nucleotide bases. (pharmacy180.com)
  • The gap left by removal of the nucleotides is filled, using the sister strand as a template, by a DNA polymerase, typically DNA pol I. The 3 I -hydroxyl of the newly synthesized DNA is joined to the 5 I -phosphate of the remaining stretch of the original DNA strand by DNA ligase. (pharmacy180.com)