An Investigation into the Acetylation of the Lyase Domain of DNA Polymerase \(\beta\) and Chromatin Structure Confers Cellular Resistance to MMS
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Johnson, Sarah Elizabeth
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CitationJohnson, Sarah Elizabeth. 2011. An Investigation into the Acetylation of the Lyase Domain of DNA Polymerase \(\beta\) and Chromatin Structure Confers Cellular Resistance to MMS. Doctoral dissertation, Harvard University.
AbstractThe methyltranferases Suv39h1 and Suv39h2 place the trimethyl mark on lysine 9 of histone H3 (H3K9me3). Heterochromatin Protein 1 (HP1) interacts with H3K9 through its chromodomain (Nielsen et al., 2001). Kap-1, another heterochromatin associated protein interacts with HP1, and together they help to form the compact heterochromatin structure. Without these methyltransferases, cells have less heterochromatin and increased genomic instability (Peters et al., 2001). Previous work in our lab (unpublished) showed that cells lacking these enzymes were more sensitive to ionizing radiation than wild type cells. This indicated a defect in double strand break repair. We wanted to ask if these cells were also more sensitive to methylating agents that cause damage that is repaired through the BER pathway. We found that cells lacking the Suv39h2 methyltransferase treated with MMS, a methylating agent, were more resistant to methylation damage than the wild type. We also wanted to ask whether Kap-1, a heterochromatin associated protein that interacts with the Suv39h1/2 methyltransferases, was phosphorylated after MMS treatment. We found ATM dependent phosphorylation of Kap-1, indicating that cells had relaxed chromatin after treatment with MMS. We hypothesize that this relaxation of chromatin gives the cells resistance to MMS as it allows for easier repair without the need for chromatin remodeling.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10275997
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