Mms22p protects Saccharomyces cerevisiae from DNA damage induced by topoisomerase II
AUTOR(ES)
Baldwin, E. L.
FONTE
Oxford University Press
RESUMO
The cleavage reaction of topoisomerase II, which creates double-stranded DNA breaks, plays a central role in both the cure and initiation of cancer. Therefore, it is important to understand the cellular processes that repair topoisomerase II-generated DNA damage. Using a genome-wide approach with Saccharomyces cerevisiae, we found that Δmre11, Δxrs2, Δrad50, Δrad51, Δrad52, Δrad54, Δrad55, Δrad57 and Δmms22 strains were hypersensitive to etoposide, a drug that specifically increases levels of topoisomerase II-mediated DNA breaks. These results confirm that the single-strand invasion pathway of homologous recombination is the major pathway that repairs topoisomerase II-induced DNA damage in yeast and also indicate an important role for Mms22p. Although Δmms22 strains are sensitive to several DNA-damaging agents, little is known about the function of Mms22p. Δmms22 cultures accumulate in G2/M, and display an abnormal cell cycle response to topoisomerase II-mediated DNA damage. MMS22 appears to function outside of the single-strand invasion pathway, but levels of etoposide-induced homologous recombination in Δmms22 cells are lower than wild-type. MMS22 is epistatic with RTT101 and RTT107, genes that encode its protein binding partners. Finally, consistent with a role in DNA processes, Mms22p localizes to discrete nuclear foci, even in the absence of etoposide or its binding partners.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=549411Documentos Relacionados
- Acidic pH induces topoisomerase II-mediated DNA damage
- The C-terminal domain of Saccharomyces cerevisiae DNA topoisomerase II.
- Analysis of functional domain organization in DNA topoisomerase II from humans and Saccharomyces cerevisiae.
- Ectopic recombination between Ty elements in Saccharomyces cerevisiae is not induced by DNA damage.
- DNA topoisomerase II mutant of Saccharomyces cerevisiae: topoisomerase II is required for segregation of daughter molecules at the termination of DNA replication.
