Graduation Year
2007
Document Type
Dissertation
Degree
Ph.D.
Degree Granting Department
Biochemistry and Molecular Biology
Major Professor
Edward Seto, Ph.D.
Co-Major Professor
Peter Medveczky, M.D.
Keywords
SIRT1, NBS1, HDAC9, ATDC, p53, Protein acetylation
Abstract
Histone deacetylases (HDACs) are a family of enzymes whose functions have been overwhelmingly associated with gene expression and chromatin dynamics by modifying the histone tails. In recent years, intensive studies have demonstrated that many non-histone proteins also could serve as substrates for HDACs. And their functions and activities have been found to be regulated by posttranslational acetylation on the ε-amino group of lysines. Here, we report that two DNA repair factors including NBS1 (Nijmegen breakage syndrome 1) and ATDC (Ataxia-Telangiectasia Group D Complementing) are acetylated proteins. SIRT1 could maintain NBS1 in a hypoacetylated state, which is required for ionizing radiation-induced NBS1 Ser343 phosphorylation. And by modulating the acetylation of ATDC, HDAC9 could prevent ATDC-p53 complex formation, promoting IR-induced cell death. These data suggest HDACs play much wider roles in cells in addition to their transcriptional repression function.
Scholar Commons Citation
Yuan, Zhigang, "Functional characterization of roles of histone deacetylases in the regulation of DNA damage response" (2007). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/2424
