title: Ribonucleotide triggered DNA damage and RNA-DNA damage responses.
abstract: Research indicates that the transient contamination of DNA with ribonucleotides exceeds all other known types of DNA damage combined. The consequences of ribose incorporation into DNA, and the identity of protein factors operating in this RNA-DNA realm to protect genomic integrity from RNA-triggered events are emerging. Left unrepaired, the presence of ribonucleotides in genomic DNA impacts cellular proliferation and is associated with chromosome instability, gross chromosomal rearrangements, mutagenesis, and production of previously unrecognized forms of ribonucleotide-triggered DNA damage. Here, we highlight recent findings on the nature and structure of DNA damage arising from ribonucleotides in DNA, and the identification of cellular factors acting in an RNA-DNA damage response (RDDR) to counter RNA-triggered DNA damage.
authors.affiliation: a Genome Integrity and Structural Biology Laboratory; National Institute of Environmental Health Sciences; NIH; DHHS ; Research Triangle Park , NC USA.
authors.forename: Bret D
authors.initials: BD
authors.lastname: Wallace
authors.forename: R Scott
authors.initials: RS
authors.lastname: Williams
mesh_terms: D000818:Animals; D004247:DNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D008958:Models, Molecular; D015394:Molecular Structure; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012265:Ribonucleotides / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: C438188:APTX protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012265:Ribonucleotides; D012313:RNA; D004247:DNA; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II
keywords: 2′-3′-cyclic PO4; AOA1; Acardi-Goutieres syndrome; Aprataxin; Aptx; Ataxia Oculomotor Apraxia; DNA adenylation; DNA damage; DNA ligase; DNA repair; Flap Endonuclease 1 (FEN-1); Genome Stability; RNA-DNA damage; RNase H2; Ribonucleotide Excision Repair (RER); Top1cc, Topoisomerase 2 (Top2); Top2cc; Topoisomerase 1 (Top1); Tyrosyl-DNA phosphodiesterase 2 (Tdp2); abortive ligation