Modifications of newly synthesized histones and the cellular response to DNA replication stress

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A broad spectrum of chemical or physical agents present in the environment can damage the genetic material of cells (DNA) and impair its functions. Indeed, DNA damage can lead to the inactivation or misregulation of important genes and ultimately cause cells to die or to behave aberrantly. Fortunately, cells possess efficient DNA repair mechanisms that allow them to mitigate the deleterious consequences of genetic lesions. In order to fit in the tiny confines of the cell, DNA is packaged into a structure called chromatin. Cells can chemically modify the basic building blocks of chromatin, which are proteins called "histones", to influence their functions. Our research program aims to use baker's yeast as a model organism to understand how chemical modifications of histone proteins influence DNA repair. We anticipate that a better understanding of these fundamental processes will unearth novel links between specific determinants of chromatin structure and the response to environmental DNA-damaging agents. Importantly, these processes generally operate in analogous manners in yeast and human cells. Our research is therefore ultimately expected to provide important clues as to the function of chromatin in maintaining the integrity of human genetic material.