The SMC5/6 complex recruits the PAF1 complex to facilitate DNA double-strand break repair

DNA double-strand break (DSB) is the most toxic form of DNA damage, which threatens genome stability and is a major cause for cancers. Homologous recombination (HR) is an error-free DSB repair pathway, in which the evolutionarily conserved SMC5/6 complex (SMC5/6C) plays essential roles. The PAF1 complex (PAF1C) is also evolutionarily conserved and is well-known to regulate transcription. Here we have shown that SMC5/6 recruits PAF1C to facilitate DSB repair. In a genetic screen for DNA Damage Response Mutants (DDRMs), we found that the Arabidopsis ddrm4 mutant is hypersensitive to DSB-inducing agents. DDRM4 encodes PAF1, a core subunit of PAF1C. Interestingly, loss of the other subunits of PAF1C also result in hypersensitivity to DSB-inducing agents. Mechanistically, SMC5/6 directly interacts with PAF1 and recruits PAF1 to DSB sites. Notably, overexpression of PAF1 partially suppresses the defects of the smc6 mutant. Moreover, we found that PAF1C facilitates DSB repair by recruiting the E2 ubiquitin-conjugating enzymes UBC1 and UBC2 and the E3 ubiquitin ligases HUB1 and HUB2, which mediate the monoubiquitination of H2B at DSB sites. Our results suggest that SMC5/6-PAF1C-UBC1/2-HUB1/2 is a new axis for DSB repair, thereby revealing a new mechanism of SMC5/6 and uncovering a new function of PAF1C.