A Systematic Analysis of Factors Localized to Damaged Chromatin Reveals PARP-Dependent Recruitment of Transcription Factors. Author Lior Izhar, Britt Adamson, Alberto Ciccia, Jedd Lewis, Laura Pontano-Vaites, Yumei Leng, Anthony Liang, Thomas Westbrook, J Wade Harper, Stephen Elledge Publication Year 2015 Type Journal Article Abstract Localization to sites of DNA damage is a hallmark of DNA damage response (DDR) proteins. To identify DDR factors, we screened epitope-tagged proteins for localization to sites of chromatin damaged by UV laser microirradiation and found >120 proteins that localize to damaged chromatin. These include the BAF tumor suppressor complex and the amyotrophic lateral sclerosis (ALS) candidate protein TAF15. TAF15 contains multiple domains that bind damaged chromatin in a poly-(ADP-ribose) polymerase (PARP)-dependent manner, suggesting a possible role as glue that tethers multiple PAR chains together. Many positives were transcription factors; > 70% of randomly tested transcription factors localized to sites of DNA damage, and of these, ∼90% were PARP dependent for localization. Mutational analyses showed that localization to damaged chromatin is DNA-binding-domain dependent. By examining Hoechst staining patterns at damage sites, we see evidence of chromatin decompaction that is PARP dependent. We propose that PARP-regulated chromatin remodeling at sites of damage allows transient accessibility of DNA-binding proteins. Keywords Humans, Transcription Factors, HEK293 Cells, Fluorescent Antibody Technique, DNA Damage, Chromatin, Chromatin Assembly and Disassembly, DNA Repair, Poly(ADP-ribose) Polymerases Journal Cell Rep Volume 11 Issue 9 Pages 1486-500 Date Published 2015 Jun 09 ISSN Number 2211-1247 DOI 10.1016/j.celrep.2015.04.053 Alternate Journal Cell Rep PMCID PMC4464939 PMID 26004182 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML