Phosphorylated hMSH6: DNA mismatch versus DNA damage recognition.

ABSTRACT: DNA mismatch repair (MMR) maintains genomic integrity by correction of mispaired bases and insertion-deletion loops. The MMR pathway can also trigger a DNA damage response upon binding of MutSα to specific DNA lesions such as O(6)methylguanine (O(6)meG). Limited information is available regarding cellular regulation of these two different pathways. Within this report, we demonstrate that phosphorylated hMSH6 increases in concentration in the presence of a G:T mismatch, as compared to an O(6)meG:T lesion. TPA, a kinase activator, enhances the phosphorylation of hMSH6 and binding of hMutSα to a G:T mismatch, though not to O(6)meG:T. UCN-01, a kinase inhibitor, decreases both phosphorylation of hMSH6 and binding of hMutSα to G:T and O(6)meG:T. HeLa MR cells, pretreated with UCN-01 and exposed

SUBMITTER: Kaliyaperumal S 

PROVIDER: S-EPMC3010429 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature