RRC ID 4209
Author Barber LJ, Youds JL, Ward JD, McIlwraith MJ, O'Neil NJ, Petalcorin MI, Martin JS, Collis SJ, Cantor SB, Auclair M, Tissenbaum H, West SC, Rose AM, Boulton SJ.
Title RTEL1 maintains genomic stability by suppressing homologous recombination.
Journal Cell
Abstract Homologous recombination (HR) is an important conserved process for DNA repair and ensures maintenance of genome integrity. Inappropriate HR causes gross chromosomal rearrangements and tumorigenesis in mammals. In yeast, the Srs2 helicase eliminates inappropriate recombination events, but the functional equivalent of Srs2 in higher eukaryotes has been elusive. Here, we identify C. elegans RTEL-1 as a functional analog of Srs2 and describe its vertebrate counterpart, RTEL1, which is required for genome stability and tumor avoidance. We find that rtel-1 mutant worms and RTEL1-depleted human cells share characteristic phenotypes with yeast srs2 mutants: lethality upon deletion of the sgs1/BLM homolog, hyperrecombination, and DNA damage sensitivity. In vitro, purified human RTEL1 antagonizes HR by promoting the disassembly of D loop recombination intermediates in a reaction dependent upon ATP hydrolysis. We propose that loss of HR control after deregulation of RTEL1 may be a critical event that drives genome instability and cancer.
Volume 135(2)
Pages 261-71
Published 2008-10-17
DOI 10.1016/j.cell.2008.08.016
PII S0092-8674(08)01061-1
PMID 18957201
PMC PMC3726190
MeSH Animals Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* DNA / metabolism DNA Helicases / genetics DNA Helicases / metabolism* DNA Repair Genomic Instability* Humans Mutation Recombination, Genetic* Saccharomyces cerevisiae / enzymology Saccharomyces cerevisiae Proteins / metabolism
IF 36.216
Times Cited 236
C.elegans tm1866