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

Fengshan Liang, Simonne Longerich, Adam S. Miller, Caroline Tang, Olga Buzovetsky, Yong Xiong, David G. Maranon, Claudia Wiese, Gary M. Kupfer, Patrick Sung

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2118-2126
Number of pages9
JournalCell Reports
Issue number10
StatePublished - Jun 7 2016
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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