• lesions
  • AP sites are pre-mutagenic lesions that can prevent normal DNA replication so the cell contains systems to identify and repair such sites. (abnova.com)
  • AP sites are pre-mutagenic lesions that can prevent normal DNA replication. (wikipedia.org)
  • To counteract this threat, cells have evolved a series of intricate DNA repair pathways that correct DNA lesions affecting base pairing or structure of DNA. (slideshare.net)
  • One of the most frequent lesions formed in cellular DNA are abasic (apurinic/apyrimidinic, AP) sites that are both cytotoxic and mutagenic, and must be removed efficiently to maintain genetic stability. (biomedsearch.com)
  • TCR can preferentially remove the bulky DNA lesions located at the transcribed strand of a transcriptional active gene more rapidly than those at the untranscribed strand or overall genomic DNA. (biomedcentral.com)
  • For example, incorporation of adenine across from 8-oxoguanine (right) during DNA replication causes a G:C base pair to be mutated to T:A. Other examples of base lesions repaired by BER include: Oxidized bases: 8-oxoguanine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG, FapyA) Alkylated bases: 3-methyladenine, 7-methylguanosine Deaminated bases: hypoxanthine formed from deamination of adenine. (wikipedia.org)
  • Thymidine products following deamination of 5-methylcytosine are more difficult to recognize, but can be repaired by mismatch-specific glycosylases) Uracil inappropriately incorporated in DNA or formed by deamination of cytosine In addition to base lesions, the downstream steps of BER are also utilized to repair single-strand breaks. (wikipedia.org)
  • Some lesions, such as oxidized or reduced AP sites, are resistant to pol β lyase activity and, therefore, must be processed by long-patch BER. (wikipedia.org)
  • Besides opening AP sites, they possess 3' phosphodiesterase activity and can remove a variety of 3' lesions including phosphates, phosphoglycolates, and aldehydes. (wikipedia.org)
  • NEIL1 (show NEIL1 ELISA Kits ) and NEIL2 are essential in the recognition of oxidized lesions arising from 8-oxoG and may play important roles in the repair of DNA damage induced by carcinogenic metals. (antibodies-online.com)
  • APE1
  • APE1 is a gene that codes for DNA AP lyase in humans which binds to AP DNA loops into both the DNA major and minor grooves and binds a flipped-out AP site in a pocket that excludes DNA bases and racemized-anomer AP sites. (wikipedia.org)
  • Meanwhile, an Asp210 in the active site, which is made more reactive due to the increase in its pKa (or the negative log of acid dissociation constant) caused through its stabilization through its hydrogen bonding between Asn68 and Asn212, activates the nucleophile that attacks and cleaves the phosphodiester backbone and probably results in the observed maximal APE1 activity at a pH of 7.5. (wikipedia.org)
  • Both also contain lots of H-bond acceptors which may interact with the H-bond donors in the active site of APE1, causing these inhibitors to stick in the active site and preventing the enzyme from catalyzing other reactions. (wikipedia.org)
  • We determined the specificity of this small molecular weight inhibitor for Pol-β by using in vitro activities of APE1, Fen1, DNA ligase I, and Pol-β-directed single-nucleotide and long-patch BER. (aacrjournals.org)
  • It blocked Pol-β-directed single-nucleotide and long-patch BER without affecting the activity of APE1, Fen1, and DNA ligase I. Fluorescence anisotropy data suggested that NSC-666715 directly and specifically interacts with Pol-β and interferes with binding to damaged DNA. (aacrjournals.org)
  • sequence
  • A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 12.7-28.0 min region on the linkage map. (waw.pl)
  • 42. A polypeptide comprising a first amino acid sequence substantially identical to SEQ ID NO:1 linked to a second amino acid sequence substantially identical to SEQ ID NO:2, wherein the first and second amino acid sequences are linked directly or by a linker having between 1-300 amino acids and wherein the polypeptide excises methylated cytosines in DNA when contacted to DNA comprising methylated cytosines. (patentsencyclopedia.com)
  • bases
  • Apurinic/apyrimidinic (AP) sites occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. (abnova.com)
  • This active site is bordered by Phe266, Trp280, and Leu282, which pack tightly with the hydrophobic side of the AP site, discriminating against sites that do have bases. (wikipedia.org)
  • Acts as DNA glycosylase that recognizes and removes damaged bases. (waw.pl)
  • Removes damaged bases from DNA, leaving an abasic site. (waw.pl)
  • Damaged bases in DNA occur due to alkylating agents, ionizing radiation or oxidants such as superoxide radicals, hydrogen peroxide and hydroxyl radicals. (waw.pl)
  • Free radical-mediated DSBs typically bear unligatable 3′-phosphate or 3′-phosphoglycolate termini and often have oxidized bases and/or abasic sites near the break. (hindawi.com)
  • BER is important for removing damaged bases that could otherwise cause mutations by mispairing or lead to breaks in DNA during replication. (wikipedia.org)
  • BER is initiated by DNA glycosylases, which recognize and remove specific damaged or inappropriate bases, forming AP sites. (wikipedia.org)
  • Single bases in DNA can be chemically damaged by a variety of mechanisms, the most common ones being deamination, oxidation, and alkylation. (wikipedia.org)
  • cellular
  • In aerobic organisms, cellular DNA is frequently damaged by activated oxygen species from aerobic energy metabolism or oxidative stress. (embopress.org)
  • Cellular genomic DNA constantly suffers from damage induced by various external genotoxic agents and endogenous metabolic materials. (biomedcentral.com)
  • activity
  • Mn2+ stabilizes the reaction of the lyase activity. (wikipedia.org)
  • DNA AP lyase activity is documented to have similar function in both E. Coli and in humans. (wikipedia.org)
  • Mutation K241Q completely abolishes DNA glycosylase activity and covalent complex formation in the presence of NaBH4. (pubmedcentralcanada.ca)
  • One possible mechanistic hypothesis is that DNA-PKcs may function through associating with CyclinT2/CDK9 (P-TEFb) to modulate the activity of RNA Pol II, which has already been identified as a key molecule recognizing and initializing TCR. (biomedcentral.com)
  • Reaction of cisplatin with purines to form DNA monoadducts that can mediate intrastrand and interstrand cross-links is essential for its cytotoxic activity ( 22 ). (aacrjournals.org)
  • phosphate
  • The AP site is then further stabilized through hydrogen bonding of the phosphate group 5´ to the AP site with Asn174, Asn212, His309, and the Mg2+ ion while its orphan base partner is stabilized through hydrogen bonding with Met270. (wikipedia.org)
  • The phosphate group 3' to the AP site is stabilized through hydrogen bonding to Arg177. (wikipedia.org)
  • First, the Asp210 residue in the active site deprotonates a water molecule, which can then perform a nucleophilic attack on the phosphate group located 5´ to the AP site. (wikipedia.org)
  • Next, electrons from one of the oxygen atom in the phosphate group moves down, kicking off one of the other oxygen to create a free 5´ phosphate group on the AP site and a free 3´-OH on the normal nucleotide, both of which are stabilized by the Mg2+ ion. (wikipedia.org)
  • The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate. (waw.pl)
  • Some glycosylase-lyases can further perform δ-elimination, which converts the 3' aldehyde to a 3' phosphate. (wikipedia.org)
  • 1993
  • Lindahl T (1993) Instability and decay of the primary structure of DNA. (els.net)
  • HeLa
  • Although depletion of DNA-PKcs sensitized HeLa cells to UV radiation, it did not affect the ggNER efficiency of UV-induced cyclobutane pyrimidine dimers (CPD) damage. (biomedcentral.com)
  • occur
  • Paul Modrich has demonstrated how the cell corrects errors that occur when DNA is replicated during cell division. (slideshare.net)
  • possess
  • Both of these structures possess rings attached to short chains, which appear similar to the deoxyribose sugar ring without a base attached and phosphodiester bond in DNA. (wikipedia.org)
  • damage
  • DNA damage is ubiquitous amongst all forms of life. (wikipedia.org)
  • 2. 1 (15) The Royal Swedish Academy of Sciences has decided to award Tomas Lindahl, Paul Modrich and Aziz Sancar the Nobel Prize in Chemistry 2015 for their "Mechanistic studies of DNA repair" Damage to the genetic material poses a threat to all organisms. (slideshare.net)
  • T . A transversions in Saccharomyces cerevisiae: evidence for endogenous oxidative damage to DNA in eukaryotic cells. (pubmedcentralcanada.ca)
  • The balance between DNA damage and repair determines the final therapeutic consequences of these drugs. (aacrjournals.org)
  • Reactive oxygen species (ROS)-induced nuclear and mitochondrial DNA damage is associated with the aging process as well as numerous pathologies in humans ( 1 ). (aacrjournals.org)
  • mutation
  • If left unrepaired, AP sites can lead to mutation during semiconservative replication. (wikipedia.org)
  • In humans, defective 8-oxodG repair may increase susceptibility to cancer, as increased ROS-associated DNA alteration and mutation is thought to promote tumor initiation and progression. (aacrjournals.org)
  • replication
  • Although very efficient, the DNA replication machinery responsible for this task still makes occasional mistakes. (slideshare.net)
  • transcription
  • Data on the participation of YB-1 in DNA reparation and transcription, mRNA splicing and translation are systematized. (semanticscholar.org)
  • By means of immunoprecipitation and MALDI-TOF-Mass spectrometric analysis, we have revealed the interaction of DNA-PKcs and cyclin T2, which is a subunit of the human transcription elongation factor (P-TEFb). (biomedcentral.com)
  • vitro
  • Much of the seminal work elucidating these repair systems has taken advantage of defined DSB substrates, either constructed in vitro or formed in cells by site-specific nucleases [ 9 ]. (hindawi.com)
  • The effect of NSC-666715 on the cytotoxicity of the DNA-alkylating drug temozolomide (TMZ) to colon cancer cells was determined by in vitro clonogenic and in vivo xenograft assays. (aacrjournals.org)
  • Repairs oxidative DNA damages in vitro. (genesilico.pl)