title: End-damage-specific proteins facilitate recruitment or stability of X-ray cross-complementing protein 1 at the sites of DNA single-strand break repair.
abstract: Ionizing radiation, oxidative stress and endogenous DNA-damage processing can result in a variety of single-strand breaks with modified 5' and/or 3' ends. These are thought to be one of the most persistent forms of DNA damage and may threaten cell survival. This study addresses the mechanism involved in recognition and processing of DNA strand breaks containing modified 3' ends. Using a DNA-protein cross-linking assay, we followed the proteins involved in the repair of oligonucleotide duplexes containing strand breaks with a phosphate or phosphoglycolate group at the 3' end. We found that, in human whole cell extracts, end-damage-specific proteins (apurinic/apyrimidinic endonuclease 1 and polynucleotide kinase in the case of 3' ends containing phosphoglycolate and phosphate, respectively) which recognize and process 3'-end-modified DNA strand breaks are required for efficient recruitment of X-ray cross-complementing protein 1-DNA ligase IIIalpha heterodimer to the sites of DNA repair.
authors.affiliation: MRC Radiation and Genome Stability Unit, Harwell, Oxon, UK.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Parsons
authors.forename: Irina I
authors.initials: II
authors.lastname: Dianova
authors.forename: Emma
authors.initials: E
authors.lastname: Boswell
authors.forename: Michael
authors.initials: M
authors.lastname: Weinfeld
authors.forename: Grigory L
authors.initials: GL
authors.lastname: Dianov
mesh_terms: D000626:Aminopeptidases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D001483:Base Sequence; D019921:Biotinylation; D002457:Cell Extracts; D003172:Complement C1 / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology; D004249:DNA Damage; D011088:DNA Ligases / Q000378:metabolism; D019951:DNA Polymerase beta / Q000378:metabolism; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000187:drug effects / Q000528:radiation effects; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism*; D043223:Deoxyribonuclease IV (Phage T4-Induced) / Q000235:genetics / Q000378:metabolism; D005557:Formaldehyde / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008280:Magnetics; D008863:Microspheres; D008954:Models, Biological; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism; D011116:Polynucleotide 5'-Hydroxyl-Kinase / Q000378:metabolism*; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D019809:Streptavidin / Q000378:metabolism; D013379:Substrate Specificity; D014965:X-Rays
chemical_list: D002457:Cell Extracts; D003172:Complement C1; D003432:Cross-Linking Reagents; D004277:DNA, Single-Stranded; D009841:Oligonucleotides; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D005557:Formaldehyde; D019809:Streptavidin; D011116:Polynucleotide 5'-Hydroxyl-Kinase; D019951:DNA Polymerase beta; D043223:Deoxyribonuclease IV (Phage T4-Induced); D000626:Aminopeptidases; C019689:APE1 protein, S cerevisiae; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D011088:DNA Ligases