title: DGCR8 Mediates Repair of UV-Induced DNA Damage Independently of RNA Processing.
abstract: Ultraviolet (UV) radiation is a carcinogen that generates DNA lesions. Here, we demonstrate an unexpected role for DGCR8, an RNA binding protein that canonically functions with Drosha to mediate microRNA processing, in the repair of UV-induced DNA lesions. Treatment with UV induced phosphorylation on serine 153 (S153) of DGCR8 in both human and murine cells. S153 phosphorylation was critical for cellular resistance to UV, the removal of UV-induced DNA lesions, and the recovery of RNA synthesis after UV exposure but not for microRNA expression. The RNA-binding and Drosha-binding activities of DGCR8 were not critical for UV resistance. DGCR8 depletion was epistatic to defects in XPA, CSA, and CSB for UV sensitivity. DGCR8 physically interacted with CSB and RNA polymerase II. JNKs were involved in the UV-induced S153 phosphorylation. These findings suggest that UV-induced S153 phosphorylation mediates transcription-coupled nucleotide excision repair of UV-induced DNA lesions in a manner independent of microRNA processing.
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA 98109-1024, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA 98109-1024, USA; Molecular and Cellular Biology Graduate Program, University of Washington, 1959 NE Pacific, HSB T-466, Seattle, WA 98195-7275, USA.
authors.forename: Philamer C
authors.initials: PC
authors.lastname: Calses
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA 98109-1024, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA 98109-1024, USA.
authors.forename: Kiranjit K
authors.initials: KK
authors.lastname: Dhillon
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA 98109-1024, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA 98109-1024, USA.
authors.forename: Nyka
authors.initials: N
authors.lastname: Tucker
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA 98109-1024, USA; Division of Clinical Research, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA 98109-1024, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chi
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA 98109-1024, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA 98109-1024, USA; Molecular and Cellular Biology Graduate Program, University of Washington, 1959 NE Pacific, HSB T-466, Seattle, WA 98195-7275, USA.
authors.forename: Jen-Wei
authors.initials: JW
authors.lastname: Huang
authors.affiliation: Division of Dermatology, Department of Medicine, University of Washington, 850 Republican St., Seattle, WA 98109-4714, USA.
authors.forename: Masaoki
authors.initials: M
authors.lastname: Kawasumi
authors.affiliation: Division of Dermatology, Department of Medicine, University of Washington, 850 Republican St., Seattle, WA 98109-4714, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Nghiem
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA 98109-1024, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA 98109-1024, USA.
authors.forename: Yemin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA 98109-1024, USA; Division of Clinical Research, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA 98109-1024, USA.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Clurman
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA 98109-1024, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA 98109-1024, USA.
authors.forename: Celine
authors.initials: C
authors.lastname: Jacquemont
authors.affiliation: Proteomics Core Facility, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., DE-352, Seattle, WA 98109-1024, USA.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Gafken
authors.affiliation: Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo 657-8501, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sugasawa
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Yamadaoka 1-3, Suita, Osaka 565-0871, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Saijo
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA 98109-1024, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA 98109-1024, USA; Department of Molecular Life Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan. Electronic address: ttaniguc@fhcrc.org.
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000378:metabolism; D000873:Anthracenes / Q000378:metabolism; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D010766:Phosphorylation; D012319:RNA Polymerase II / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D000873:Anthracenes; C474043:DGCR8 protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C432165:pyrazolanthrone; D000841:Anisomycin; D004247:DNA; D048670:MAP Kinase Kinase 4; D012319:RNA Polymerase II; C517918:DROSHA protein, human; D043244:Ribonuclease III
keywords: DGCR8; DNA repair; Drosha; JNK; UV radiation; microRNA; transcription-coupled nucleotide excision repair