作者: Nimna S. Ranatunga , Susan L. Forsburg
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摘要: The minichromosome maintenance (MCM) complex is the conserved helicase motor of eukaryotic replication fork. Mutations in Mcm4 subunit are associated with stress and double strand breaks multiple systems. In this work, we characterize a new temperature-sensitive allele Schizosaccharomyces pombe mcm4+ . Uniquely among known mcm4 alleles, mutation causes sensitivity to alkylation damaging agent methyl methanesulfonate (MMS). Even absence treatment or temperature shift, mcm4-c106 cells show increased repair foci RPA Rad52, require damage checkpoint for viability, indicating genome stress. mutant synthetically lethal mutations disrupting fork protection (FPC) proteins Swi1 Swi3. Surprisingly, found that deletion rif1+ suppressed MMS-sensitive phenotype without affecting sensitivity. Together, these data suggest destabilizes replisome structure.