The research of my laboratory focuses on the molecular mechanism of cell cycle checkpoint activation. Cell cycle checkpoint is a self-defense system of cells. When cells encounter external or internal hazards, such as X-ray, UV, DNA replication errors or mitotic stress, cell cycle checkpoint senses…
more DNA lesions generated by these hazards, and stops cell cycle progression. It allows cells having enough time to correct these lesions before proceeding to the next round of cell cycle. Loss of cell cycle checkpoints will disrupt repair process, trigger genomic instability, and ultimately lead to tumorigenesis. One typical example is BRCA1, which not only functions as an important player in DNA damage response but also is breast tumor suppressor. During past few years, my lab and others have identified a unique protein ubiquitination cascade induced by DNA double strand breaks. This ubiquitination cascade does not target proteins for degradation. Instead, like protein phosphorylation, this ubiquitination cascade functions in the DNA damage-induced signaling network for amplification of damage signals, which activates cell cycle checkpoint and DNA damage repair. Currently, by using various in vitro and in vivo approaches, we are dissecting the roles of several key players, including BRCA1, in this novel pathway.
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