MUS81-EME2 promotes replication fork restart
- Cell Rep. 2014 May 22;7(4):1048-55. doi: 10.1016/j.celrep.2014.04.007.
- 1. London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK.
- 2. London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK. Electronic address: [email protected].
Replication forks frequently stall at regions of the genome that are difficult to replicate or contain lesions that cause replication blockage. An important mechanism for the restart of a stalled fork involves endonucleolytic cleavage that can lead to fork restoration and replication progression. Here, we show that the structure-selective Endonuclease MUS81-EME2 is responsible for fork cleavage and restart in human cells. The MUS81-EME2 protein, whose actions are restricted to S phase, is also responsible for telomere maintenance in telomerase-negative ALT (Alternative Lengthening of Telomeres) cells. In contrast, the G2/M functions of MUS81, such as the cleavage of recombination intermediates and fragile site expression, are promoted by MUS81-EME1. These results define distinct and temporal roles for MUS81-EME1 and MUS81-EME2 in the maintenance of genome stability.