title: MUS81-EME2 promotes replication fork restart.
abstract: 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.
authors.affiliation: London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pepe
authors.affiliation: London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK. Electronic address: stephen.west@cancer.org.uk.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: West
mesh_terms: D045744:Cell Line, Tumor; D004247:DNA / Q000096:biosynthesis*; D004261:DNA Replication / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000235:genetics* / Q000378:metabolism*; D004720:Endonucleases / Q000235:genetics* / Q000378:metabolism*; D042822:Genomic Instability; D006367:HeLa Cells; D006801:Humans; D021122:Protein Subunits; D016196:S Phase / Q000502:physiology; D016615:Telomere / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D021122:Protein Subunits; D004247:DNA; C000588977:EME2 protein, human; D004706:Endodeoxyribonucleases; D004720:Endonucleases; C498772:MUS81 protein, human