Hoi-Man Ng

Protein ubiquitination has emerged as a pivotal regulatory reaction that promotes cellular responses to DNA damage. With a goal to delineate the DNA damage signal transduction cascade, we systematically analyzed the human E2 ubiquitin- and ubiquitin-like-conjugating enzymes for their ability to mobilize the DNA damage marker 53BP1 onto ionizing radiation-induced DNA double strand breaks. An RNAi-based screen identified UBE2U as a candidate regulator of chromatin responses at double strand breaks.

Author contributions: MSYH and SMHS conceptualized and supervised the project. YG and LA performed all the experiments with help from HMN and SMHS. MSYH, SMHS and YG analysed the data. YG and MSYH drafted the manuscript. HMN designed the cartoon illustration. All authors reviewed the results and approved the final version of the manuscript. Protein ubiquitination has emerged as pivotal regulatory reactions that promote cellular responses to DNA damage.

Multisubunit protein assemblies offer integrated functionalities for efficient cell signal transduction control. One example of such protein assemblies, the BRCA1-A macromolecular complex, couples ubiquitin recognition and metabolism and promotes cellular responses to DNA damage. Specifically, the BRCA1-A complex not only recognizes Lys63-linked ubiquitin (K63-Ub) adducts at the damaged chromatin but is endowed with K63-Ub deubiquitylase (DUB) activity.