RRC ID 35576
著者 Smogorzewska A, Desetty R, Saito TT, Schlabach M, Lach FP, Sowa ME, Clark AB, Kunkel TA, Harper JW, Colaiácovo MP, Elledge SJ.
タイトル A genetic screen identifies FAN1, a Fanconi anemia-associated nuclease necessary for DNA interstrand crosslink repair.
ジャーナル Mol Cell
Abstract The Fanconi anemia (FA) pathway is responsible for interstrand crosslink repair. At the heart of this pathway is the FANCI-FAND2 (ID) complex, which, upon ubiquitination by the FA core complex, travels to sites of damage to coordinate repair that includes nucleolytic modification of the DNA surrounding the lesion and translesion synthesis. How the ID complex regulates these events is unknown. Here we describe a shRNA screen that led to the identification of two nucleases necessary for crosslink repair, FAN1 (KIAA1018) and EXDL2. FAN1 colocalizes at sites of DNA damage with the ID complex in a manner dependent on FAN1's ubiquitin-binding domain (UBZ), the ID complex, and monoubiquitination of FANCD2. FAN1 possesses intrinsic 5'-3' exonuclease activity and endonuclease activity that cleaves nicked and branched structures. We propose that FAN1 is a repair nuclease that is recruited to sites of crosslink damage in part through binding the ubiquitinated ID complex through its UBZ domain.
巻・号 39(1)
ページ 36-47
公開日 2010-7-9
DOI 10.1016/j.molcel.2010.06.023
PII S1097-2765(10)00464-8
PMID 20603073
PMC PMC2919743
MeSH Amino Acid Sequence Animals Caenorhabditis elegans / metabolism Cell Line Cross-Linking Reagents / metabolism* DNA Damage DNA Mismatch Repair / drug effects DNA Repair* / drug effects Endodeoxyribonucleases Endonucleases / metabolism Exodeoxyribonucleases / chemistry Exodeoxyribonucleases / metabolism* Exonucleases / chemistry Exonucleases / metabolism* Fanconi Anemia / enzymology* Fanconi Anemia / pathology Fanconi Anemia Complementation Group D2 Protein / metabolism Genetic Testing / methods* Genome, Human / genetics Humans Mitomycin / pharmacology Molecular Sequence Data Multifunctional Enzymes Protein Binding / drug effects Protein Structure, Tertiary Protein Transport / drug effects RNA, Small Interfering / metabolism
IF 15.584
引用数 226
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
線虫 tm423