Genome-Wide Histone Acetylation and the DNA Damage Response
题目：Genome-Wide Histone Acetylation and the DNA Damage Response
讲座人： Alain Verreault，Ph.D.
Institute for Research in Immunology and Cancer (IRIC),
Univ. Montreal, Canada
时间：2017年4月21日，13:00 - 14:30
Numerous DNA lesions that occur spontaneously and DNA lesions caused by environmental carcinogens or cancer chemotherapeutic agents interfere with the completion of DNA replication. The links between the repair of DNA lesions that impair replication and chromatin structure are poorly understood. For many years, our laboratory has been studying a fascinating feature of the "chromosome cycle". During DNA replication, newly synthesized histones are rapidly deposited onto nascent DNA to restore chromatin structure. In the budding yeast Saccharomyces cerevisiae, we showed that essentially all the new histone H3 molecules deposited throughout the genome are acetylated at lysine 56 (H3-K56). In the absence of persistent DNA lesions, H3-K56 is deacetylated from the entire genome during G2/M phase of the cell cycle. Thus, genome-wide cycles of H3-K56 acetylation and deacetylation create transient waves of histone acetylation that sweep throughout the genome during each passage through the cell cycle. Mutant cells that cannot acetylate or deacetylate H3-K56 exhibit persistent spontaneous DNA lesions and are exquisitely sensitive to chemicals that damage DNA during replication. We present several lines of evidence suggesting that the acute sensitivity to DNA damage of mutants in which the H3-K56 acetylation cycle is perturbed stems from mitotic segregation of incompletely duplicated DNA.
After completing his Ph.D. at the University of Cambridge, Professor Alain Verreault conducted postdoctoral research at Cold Spring Harbor Laboratory. In 1999, he established his own laboratory at the Imperial Cancer Research Fund Clare Hall Laboratories (now known as Cancer Research UK). At the end of 2005, his laboratory moved to the Institute for Research in Immunology and Cancer (IRIC, Univ. Montreal, Canada: www.iric.ca/en/). At the University of Montreal, he is Professor in the Department of Pathology and Cell Biology and holds a Canada Research Chair in Nucleosome Assembly and Genome Integrity. Throughout his career, Professor Verreault has been interested in the enzymes and molecular mechanisms involved in the first step of chromosome biogenesis, namely the assembly of nucleosomes onto nascent DNA during replication. Among other findings, his laboratory has uncovered unexpected links between nucleosome assembly and the ability of cells to survive DNA damage caused by environmental carcinogens or cancer chemotherapeutic agents.