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 journalArticle

21 Scopus citations

Abstract

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
Volume15
Issue number10
DOIs
StatePublished - Jun 7 2016
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Liang, F., Longerich, S., Miller, A. S., Tang, C., Buzovetsky, O., Xiong, Y., Maranon, D. G., Wiese, C., Kupfer, G. M., & Sung, P. (2016). Promotion of RAD51-Mediated Homologous DNA Pairing by the RAD51AP1-UAF1 Complex. Cell Reports, 15(10), 2118-2126. https://doi.org/10.1016/j.celrep.2016.05.007