Promotion of RAD51-Mediated Homologous DNA Pairing by the RAD51AP1-UAF1 Complex

作者：Liang Fengshan; Longerich Simonne; Miller Adam S; Tang Caroline; Buzovetsky Olga; Xiong Yong; Maranon David G; Wiese Claudia; Kupfer Gary M^*; Sung Patrick^*

来源：Cell Reports, 2016, 15(10): 2118-2126.

DOI：10.1016/j.celrep.2016.05.007

The UAF1-USP1 complex deubiquitinates FANCD2 during execution of the Fanconi anemia DNA damage response pathway. As such, UAF1 depletion results in persistent FANCD2 ubiquitination and DNA damage hypersensitivity. UAF1-deficient cells are also impaired for DNA repair by homologous recombination. Herein, we show that UAF1 binds DNA and forms a dimeric complex with RAD51AP1, an accessory factor of the RAD51 recombinase, and a trimeric complex with RAD51 through RAD51AP1. Two small ubiquitin-like modifier (SUMO)-like domains in UAF1 and a SUMO-interacting motif in RAD51AP1 mediate complex formation. Importantly, UAF1 enhances RAD51-mediated homologous DNA pairing in a manner that is dependent on complex formation with RAD51AP1 but independent of USP1. Mechanistically, RAD51AP1-UAF1 co-operates with RAD51 to assemble the synaptic complex, a critical nucleoprotein intermediate in homologous recombination, and cellular studies reveal the biological significance of the RAD51AP1-UAF1 protein complex. Our findings provide insights into an apparently USP1-independent role of UAF1 in genome maintenance.

• 出版日期2016-6-7