Title

RTEL1 maintains genomic stability by suppressing homologous recombination

UMMS Affiliation

Program in Gene Function and Expression; Department of Cancer Biology

Date

10-30-2008

Document Type

Article

Medical Subject Headings

Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; DNA; DNA Helicases; DNA Repair; *Genomic Instability; Humans; Mutation; *Recombination, Genetic; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins

Disciplines

Cancer Biology | Genetics and Genomics

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.

Rights and Permissions

Citation: Cell. 2008 Oct 17;135(2):261-71. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

18957201