title: INO80 chromatin remodeling complex promotes the removal of UV lesions by the nucleotide excision repair pathway.
abstract: The creation of accessible DNA in the context of chromatin is a key step in many DNA functions. To reveal how ATP-dependent chromatin remodeling activities impact DNA repair, we constructed mammalian genetic models for the INO80 chromatin remodeling complex and investigated the impact of loss of INO80 function on the repair of UV-induced photo lesions. We showed that deletion of two core components of the INO80 complex, INO80 and ARP5, significantly hampered cellular removal of UV-induced photo lesions but had no significant impact on the transcription of nucleotide excision repair (NER) factors. Loss of INO80 abolished the assembly of NER factors, suggesting that prior chromatin relaxation is important for the NER incision process. Ino80 and Arp5 are enriched to UV-damaged DNA in an NER-incision-independent fashion, suggesting that recruitment of the remodeling activity likely takes place during the initial stage of damage recognition. These results demonstrate a critical role of INO80 in creating DNA accessibility for the NER pathway and provide direct evidence that repair of UV lesions and perhaps most bulky adduct lesions requires chromatin reconfiguration.
authors.affiliation: Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Shilai
authors.initials: S
authors.lastname: Bao
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Guo
authors.forename: David G
authors.initials: DG
authors.lastname: Johnson
authors.forename: Xuetong
authors.initials: X
authors.lastname: Shen
authors.forename: Lei
authors.initials: L
authors.lastname: Li
mesh_terms: D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D055785:Gene Knockdown Techniques; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: C483404:INO80 complex, S cerevisiae; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA