A role for Mus81 in the repair of chromium-induced DNA damage

作者：Tamblyn Laura; Li Erica; Sarras Haya; Srikanth Prarthana; Hande M Prakash; McPherson J Peter^*

来源：Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, 2009, 660(1-2): 57-65.

DOI：10.1016/j.mrfmmm.2008.10.013

• Mus81
• Eme1
• Chromium[VI]
• Rad51
• gamma-112AX
• Chromosomal instability

Hexavalent chromium (Cr[VI]) is a toxic environmental contaminant that is capable of producing a broad spectrum of DNA damage. The ability of Cr[VI] to induce mutagenesis and neoplastic transformation has been attributed to its genotoxic action, however Out Understanding of molecular mechanisms involved in the repair of Cr[VI]-induced DNA damage remains incomplete. Here, we report that Mus81, an enzyme that participates with Eme1 in the resolution of replication fork damage caused by certain lesions, is involved in the repair of Cr[VI]-induced DNA damage. Mus81-deficient cells were found to be more Susceptible to Cr[VI]-induced proliferation arrest and more sensitive to the long-term cytotoxic effects of Cr[VI] than isogenic wild-type cells. Following Cr[VI] exposure, Mus81-deficient cells displayed a lag in the disappearance of Rad51 foci, exhibited elevated replication-associated gamma-H2AX and showed in increased incidence of chromosomal instability compared to wild-type cells. Our findings support a role for Mus81 in the resolution of replication-associated DNA damage associated with this genotoxic agent, by converting Cr[VI]-DNA lesions into a form more amenable for homologous recombination.

• 出版日期2009-1-15