Xiaoyu Xue, an associate professor in the Department of Chemistry and Biochemistry at Texas State University, has received a nearly $600,000 grant from the National Institutes of Health to study the role protein sumoylation plays in DNA repair.
The four-year grant was awarded by the NIH’s National Institute of General Medical Sciences and will fund Xue’s project, “Mechanism of Smc5/6-mediated protein sumoylation in DNA repair.” This study builds upon previous sumoylation research by Xue published in the journals Genes & Development in 2021 and J Biol Chem in 2022.
Sumoylation is a cellular process that can regulate many protein functions, including repair of damage to the genome.
“One of my lab’s longterm goals is to explore how protein sumoylation regulates the function of DNA repair proteins during DNA damage repair to maintain genome stability,” Xue said. “The overall goal of this study is to determine whether DNA binding, adenosine triphosphate binding and hydrolysis activities mediated by a specific chromosome maintenance complex (Smc5/6) contribute to sumoylation efficiency and specificity, and genome stability.”
Genomic DNA is vulnerable to myriad internal and external damaging agents, such as ionizing and ultraviolet radiation, chemical carcinogens and cellular metabolites. Cells have evolved a dozen DNA repair pathways to repair these lesions efficiently. Amongst these pathways, homologous recombination (HR) is a conserved pathway for the repair of DNA double- strand breaks (DSBs) and damaged replication forks. In eukaryotic cells, HR requires tight regulation to achieve timely activation and suppression.
Sumoylation is one type of cellular regulation that can control the functions of HR proteins. Dysfunctional sumoylation in HR can lead to gross chromosomal rearrangements and cancer, according to Xue.
Currently, how different sumoylation enzymes confer sumoylation of specific HR proteins at DNA damage sites is poorly understood. Xue’s study is expected to provide insights into the mechanisms of an essential SUMO E3 complex that play pivotal roles in HR repair and genome stability, potentially leading to new therapeutic strategies for human diseases related to dysfunctional sumoylation.
