title: Transcription-coupled homologous recombination after oxidative damage.
abstract: Oxidative DNA damage induces genomic instability and may lead to mutagenesis and carcinogenesis. As severe blockades to RNA polymerase II (RNA POLII) during transcription, oxidative DNA damage and the associated DNA strand breaks have a profoundly deleterious impact on cell survival. To protect the integrity of coding regions, high fidelity DNA repair at a transcriptionally active site in non-dividing somatic cells, (i.e., terminally differentiated and quiescent/G0 cells) is necessary to maintain the sequence integrity of transcribed regions. Recent studies indicate that an RNA-templated, transcription-associated recombination mechanism is important to protect coding regions from DNA damage-induced genomic instability. Here, we describe the discovery that G1/G0 cells exhibit Cockayne syndrome (CS) B (CSB)-dependent assembly of homologous recombination (HR) factors at double strand break (DSB) sites within actively transcribed regions. This discovery is a challenge to the current dogma that HR occurs only in S/G2 cells where undamaged sister chromatids are available as donor templates.
authors.affiliation: University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Pittsburgh, PA 15213, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 523 Bridgeside Point II, 450 Technology Drive, Pittsburgh, PA 15219, USA.
authors.forename: Leizhen
authors.initials: L
authors.lastname: Wei
authors.affiliation: University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Pittsburgh, PA 15213, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 523 Bridgeside Point II, 450 Technology Drive, Pittsburgh, PA 15219, USA.
authors.forename: Arthur Samuel
authors.initials: AS
authors.lastname: Levine
authors.affiliation: University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Pittsburgh, PA 15213, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 523 Bridgeside Point II, 450 Technology Drive, Pittsburgh, PA 15219, USA. Electronic address: lil64@pitt.edu.
authors.forename: Li
authors.initials: L
authors.lastname: Lan
mesh_terms: D020137:Base Pair Mismatch; D003057:Cockayne Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D016193:G1 Phase; D042822:Genomic Instability; D059765:Homologous Recombination; D006801:Humans; D018384:Oxidative Stress; D000075223:Poly-ADP-Ribose Binding Proteins; D012319:RNA Polymerase II / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000075223:Poly-ADP-Ribose Binding Proteins; D004247:DNA; D012319:RNA Polymerase II; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes
keywords: CSB; Genome stability; Homologous recombination; RNA template; Transcription