KOSEN 한인과학기술자네트워크

Our genome is under constant surveillance for damage to its DNA. Double strand breaks (DSBs) of chromosomal DNA, the most lethal form of DNA damage, can be generated by exposure to inonizing radiation, and also naturally occur during the normal cellular processes such as DNA replication. Unless accurately and efficiently repaired, DSBs can lead to genome instability and cancer development. The DNA in our genome is compacted into nucleosomes and higher-order chromatin structure which provides an intrinsic but regulatable barrier to protein access. The process that detects chromosomal breaks and activates an intricate network of mechanisms for arresting cell cycle and repairing the breaks, collectively known as DNA damage response, therefore must occur in concert with the process that modulates chromatin structure. Indeed, it is becoming increasingly clear that remodeling of chromatin structure is an essential and intricate part of the process of DSB repair and damage response. Our research interests focus on understanding the role of chromatin remodeling and histone modifications in maintenance of genome stability and suppression of cancer development. More specifically, we aim to elucidate how chromatin remodeling complexes that alter chromatin structure using ATP-driven energy are implicated in and by what mechanisms they regulate the complex cellular network of DSB repair, cell-cycle checkpoints and apoptosis. Recently, we and others showed that several members of the SWI/SNF-based ATP-dependent chromatin remodeling complex family are directly implicated in DSB repair and cell cycle checkpoints in yeast and mammalian cells. These studies not only demonstrate a direct role for ATP-dependent chromatin remodeling in DSB repair and damage response, but they also suggest that different members of the SWI/SNF family remodeling complexes, such as SWI/SNF, INO80, Swr1 and RSC, play distinct roles in the pathways of DSB response. The goal of current research in our laboratory is to elucidate the mechanisms dictating the functional ramifications of the SWI/SNF family chromatin remodeling complexes in DSB repair and damage response. We are also interested in elucidating the mechanisms of how ATP-dependent chromatin remodeling functions in concert with histone modifications and of how these two general modes of chromatin alterations are coordinated in the regulation of DNA damage response.