RRC ID 4322
Author Youds JL, Barber LJ, Ward JD, Collis SJ, O'Neil NJ, Boulton SJ, Rose AM.
Title DOG-1 is the Caenorhabditis elegans BRIP1/FANCJ homologue and functions in interstrand cross-link repair.
Journal Mol. Cell. Biol.
Abstract Fanconi anemia (FA) is a cancer susceptibility syndrome characterized by defective DNA interstrand cross-link (ICL) repair. Here, we show that DOG-1 is the Caenorhabditis elegans homologue of FANCJ, a helicase mutated in FA-J patients. DOG-1 performs a conserved role in ICL repair, as dog-1 mutants are hypersensitive to ICL-inducing agents, but not to UVC irradiation or X rays. Genetic analysis indicated that dog-1 is epistatic with fcd-2 (C. elegans FANCD2) but is nonepistatic with brc-1 (C. elegans BRCA1), thus establishing the existence of two distinct pathways of ICL repair in worms. Furthermore, DOG-1 is dispensable for FCD-2 and RAD-51 focus formation, suggesting that DOG-1 operates downstream of FCD-2 and RAD-51 in ICL repair. DOG-1 was previously implicated in poly(G)/poly(C) (G/C) tract maintenance during DNA replication. G/C tracts remain stable in the absence of ATL-1, CLK-2 (FA pathway activators), FCD-2, BRC-2, and MLH-1 (associated FA components), implying that DOG-1 is the sole FA component required for G/C tract maintenance in a wild-type background. However, FCD-2 is required to promote deletion-free repair at G/C tracts in dog-1 mutants, consistent with a role for FA factors at the replication fork. The functional conservation between DOG-1 and FANCJ suggests a possible role for FANCJ in G/C tract maintenance in human cells.
Volume 28(5)
Pages 1470-9
Published 2008-3
DOI 10.1128/MCB.01641-07
PII MCB.01641-07
PMID 18086896
PMC PMC2258786
MeSH Amino Acid Sequence Animals Basic-Leucine Zipper Transcription Factors / genetics Basic-Leucine Zipper Transcription Factors / metabolism Basic-Leucine Zipper Transcription Factors / physiology* Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* Cross-Linking Reagents / pharmacology DNA Helicases / chemistry DNA Helicases / genetics DNA Helicases / physiology* DNA Repair / drug effects DNA Repair / genetics DNA Repair / physiology* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism DNA-Binding Proteins / physiology* Fanconi Anemia Complementation Group Proteins / genetics Fanconi Anemia Complementation Group Proteins / metabolism Fanconi Anemia Complementation Group Proteins / physiology* Immunohistochemistry Molecular Sequence Data Mutation RNA Helicases / genetics RNA Helicases / metabolism RNA Helicases / physiology* Sequence Homology, Amino Acid
IF 3.813
Times Cited 67
C.elegans tm1298 tm853 tm1086