The anaphase-promoting complex/cyclosome (APC/C) controls repair and recombination by ubiquitylating Rhp54 in fission yeast

Cell Cycle Control Laboratory, Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL, U.K.

^* To whom correspondence should be addressed. Email: h.yamano{at}mcri.ac.uk.

	Abstract

Homologous recombination (HR) is important for maintaining genome integrity and for the process of meiotic chromosome segregation and the generation of variation. HR is regulated throughout the cell cycle, being prevalent in S and G2 phase and suppressed in G1 phase. Here we show that the anaphase-promoting complex/cyclosome (APC/C) regulates homologous recombination in the fission yeast S. pombe by ubiquitylating Rhp54 (an ortholog of Rad54). We show that Rhp54 is a novel APC/C substrate that is destroyed in G1 phase in a KEN-box and Ste9/Fizzy-related manner. The biological consequences of failing to temporally regulate HR via Rhp54 degradation are seen in haploid only in the absence of anti-recombinase, Srs2 function, and are more extensive in diploid cells which become sensitive to a range of DNA damaging agents, including hydroxyurea (HU), methyl methane sulfonate (MMS), bleomycin and UV. During meiosis, expression of non-degradable Rhp54 inhibits interhomolog recombination and stimulates sister chromatid recombination. We thus propose that it is critical to control levels of Rhp54 in G1 to suppress HR repair of double strand breaks (DSBs) and during meiosis to coordinate interhomolog recombination.