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PMID: 19641493 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Specific pathways prevent duplication-mediated genome rearrangements.

Nature ·Vol. 460 ·No. 7258 ·2009-08-20 ·Pages 984-9

Putnam CD, Hayes TK, Kolodner RD

Abstract

We have investigated the ability of different regions of the left arm of Saccharomyces cerevisiae chromosome V to participate in the formation of gross chromosomal rearrangements (GCRs). We found that the 4.2-kilobase HXT13-DSF1 region sharing divergent homology with chromosomes IV, X and XIV, similar to mammalian segmental duplications, was 'at risk' for participating in duplication-mediated GCRs generated by homologous recombination. Numerous genes and pathways, including SGS1, TOP3, RMI1, SRS2, RAD6, SLX1, SLX4, SLX5, MSH2, MSH6, RAD10 and the DNA replication stress checkpoint requiring MRC1 and TOF1, were highly specific for suppressing these GCRs compared to GCRs mediated by single-copy sequences. These results indicate that the mechanisms for formation and suppression of rearrangements occurring in regions containing at-risk sequences differ from those occurring in regions of single-copy sequence. This explains how extensive genome instability is prevented in eukaryotic cells whose genomes contain numerous divergent repeated sequences.

MeSH Terms
Amino Acid Transport Systems, Basic/genetics Cell Cycle Chromosome Aberrations Chromosomes, Fungal/genetics,metabolism DNA-Directed DNA Polymerase/genetics Gene Duplication Genes, Duplicate/genetics Genome, Fungal/genetics Genotype Recombination, Genetic Saccharomyces cerevisiae/cytology,genetics,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism
Chemicals
Amino Acid Transport Systems, Basic CAN1 protein, S cerevisiae Pol32 protein, S cerevisiae Saccharomyces cerevisiae Proteins DNA-Directed DNA Polymerase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Putnam Christopher D
Ludwig Institute for Cancer Research, Department of Medicine, University of California School of Medicine, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0669, USA.
Hayes Tikvah K
Kolodner Richard D
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Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
DOI
10.1038/nature08217
Published
2009-08-20
Epub
2009-00-29
Pages
984-9
Language
English
Region
England
NLM ID
0410462
PMCID
PMC2785216
Subset
IM
Grants
NIGMS NIH HHS · R01 GM026017 · United States
NIGMS NIH HHS · R01 GM026017-33 · United States
NIGMS NIH HHS · R37 GM026017 · United States
NIGMS NIH HHS · GM26017 · United States
External Links
PubMed source DOI: 10.1038/nature08217 PMC Full Text View journal details
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