Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 23, Pages 9747-9752Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0703192104
Keywords
dsDNA break; gross chromosomal rearrangement; translesion DNA synthesis; peroxiredoxin
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Funding
- NIGMS NIH HHS [R37 GM026017, R01 GM026017, GM26017] Funding Source: Medline
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The absence of Tsa1, a key peroxiredoxin that functions to scavenge H2O2 in Saccharomyces cerevisiae, causes the accumulation of a broad spectrum of mutations including gross chromosomal rearrangements (GCRs). Deletion of TSA1 also causes synthetic lethality in combination with mutations in RAD6 and several key genes involved in DNA double-strand break repair. In the present study we investigated the causes of GCRs and cell death in these mutants. tsa1-associated GCRs were independent of the activity of the translesion DNA polymerases, zeta, eta, and Rev1. Anaerobic growth reduced substantially GCR rates of WT and tsa1 mutants and restored the viability of tsal rad6, tsal rad51, and tsa1 mre11 double mutants. Anaerobic growth also reduced the GCR rate of rad27, pif1, and rad52 mutants, indicating a role of reactive oxygen species in GCR formation in these mutants. in addition, deletion of TSA1 or H2O2 treatment of WT cells resulted in increased formation of Rad52 foci, sites of repair of multiple DNA lesions. H2O2 treatment also induced the GCRs. Our results provide in vivo evidence that oxygen metabolism and reactive oxygen species are important sources of DNA damages that can lead to GCRs and lethal effects in S. cerevisiae.
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