title: Role of polycomb group proteins in the DNA damage response--a reassessment.
abstract: A growing body of evidence suggests that Polycomb group (PcG) proteins, key regulators of lineage specific gene expression, also participate in the repair of DNA double-strand breaks (DSBs) but evidence for direct recruitment of PcG proteins at specific breaks remains limited. Here we explore the association of Polycomb repressive complex 1 (PRC1) components with DSBs generated by inducible expression of the AsiSI restriction enzyme in normal human fibroblasts. Based on immunofluorescent staining, the co-localization of PRC1 proteins with components of the DNA damage response (DDR) in these primary cells is unconvincing. Moreover, using chromatin immunoprecipitation and deep sequencing (ChIP-seq), which detects PRC1 proteins at common sites throughout the genome, we did not find evidence for recruitment of PRC1 components to AsiSI-induced DSBs. In contrast, the S2056 phosphorylated form of DNA-PKcs and other DDR proteins were detected at a subset of AsiSI sites that are predominantly at the 5' ends of transcriptionally active genes. Our data question the idea that PcG protein recruitment provides a link between DSB repairs and transcriptional repression.
authors: Molecular Oncology Laboratory, Cancer Research UK London Research Institute, London, United Kingdom.
authors: Hollie
authors: H
authors: Chandler
authors: Bioinformatics and Biostatistics Service, Cancer Research UK London Research Institute, London, United Kingdom.
authors: Harshil
authors: H
authors: Patel
authors: Molecular Oncology Laboratory, Cancer Research UK London Research Institute, London, United Kingdom.
authors: Richard
authors: R
authors: Palermo
authors: Molecular Oncology Laboratory, Cancer Research UK London Research Institute, London, United Kingdom.
authors: Sharon
authors: S
authors: Brookes
authors: Advanced Sequencing Facility, Cancer Research UK London Research Institute, London, United Kingdom.
authors: Nik
authors: N
authors: Matthews
authors: Molecular Oncology Laboratory, Cancer Research UK London Research Institute, London, United Kingdom.
authors: Gordon
authors: G
authors: Peters
mesh_terms: D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004262:DNA Restriction Enzymes / Q000235:genetics / Q000378:metabolism; D051747:DNA-Activated Protein Kinase / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D063150:Polycomb Repressive Complex 1 / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D019076:Transgenes
chemical_list: D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; D063150:Polycomb Repressive Complex 1; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D004262:DNA Restriction Enzymes