Control of Mus81 nuclease during the cell cycle

DNA replication and homologous recombination involve the formation of branched DNA structures that physically link chromosomes. Such DNA-based connections, which arise during S-phase, are typically disengaged prior to entry into mitosis, in order to ensure proper chromosome segregation. Exceptions can, however, occur: replication stress, or elevated levels of DNA damage, may cause cells to enter mitosis with unfinished replication as well as carrying recombination intermediates, such as Holliday junctions. Hence, cells are equipped with pathways that recognize and process branched DNA structures, and evolved mechanisms to enhance their function when on the verge of undergoing cell division. One of these pathways utilizes the structure-selective endonuclease Mus81, which is thought to facilitate the resolution of replication and recombination intermediates. Mus81 function is known to be enhanced upon entry into M phase in budding yeast and human cells. Based on recent findings, we discuss here an updated model of Mus81 control during the cell cycle.