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Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18196-201. Epub 2006 Nov 17.

Suppression of spontaneous genome rearrangements in yeast DNA helicase mutants.

Author information

1
Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA. kschmidt@cas.usf.edu

Abstract

Saccharomyces cerevisiae mutants lacking two of the three DNA helicases Sgs1, Srs2, and Rrm3 exhibit slow growth that is suppressed by disrupting homologous recombination. Cells lacking Sgs1 and Rrm3 accumulate gross-chromosomal rearrangements (GCRs) that are suppressed by the DNA damage checkpoint and by homologous recombination-defective mutations. In contrast, rrm3, srs2, and srs2 rrm3 mutants have wild-type GCR rates. GCR types in helicase double mutants include telomere additions, translocations, and broken DNAs healed by a complex process of hairpin-mediated inversion. Spontaneous activation of the Rad53 checkpoint kinase in the rrm3 mutant depends on the Mec3/Rad24 DNA damage sensors and results from activation of the Mec1/Rad9-dependent DNA damage response rather than the Mrc1-dependent replication stress response. Moreover, helicase double mutants accumulate Rad51-dependent Ddc2 foci, indicating the presence of recombination intermediates that are sensed by checkpoints. These findings demonstrate that different nonreplicative helicases function at the interface between replication and repair to maintain genome integrity.

PMID:
17114288
PMCID:
PMC1838729
DOI:
10.1073/pnas.0608566103
[Indexed for MEDLINE]
Free PMC Article
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