Hovik Gasparayan, Chris Caridi, Jeff Julius, Wenyi Feng, Jeff Bachant, Constance I Nugent
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Yeast Stn1 promotes MCM to circumvent Rad53 control of the S phase checkpoint.
Treating yeast cells with the replication inhibitor hydroxyurea activates the S phase checkpoint kinase Rad53, eliciting responses that block DNA replication origin firing, stabilize replication forks, and prevent premature extension of the mitotic spindle. We previously found overproduction of Stn1, a subunit of the telomere-binding Cdc13-Stn1-Ten1 complex, circumvents Rad53 checkpoint functions in hydroxyurea, inducing late origin firing and premature spindle extension even though Rad53 is activated normally. Here, we show Stn1 overproduction acts through remarkably similar pathways compared to loss of RAD53, converging on the MCM complex that initiates origin firing and forms the catalytic core of the replicative DNA helicase. First, mutations affecting Mcm2 and Mcm5 block the ability of Stn1 overproduction to disrupt the S phase checkpoint. Second, loss of function stn1 mutations compensate rad53 S phase checkpoint defects. Third Stn1 overproduction suppresses a mutation in Mcm7. Fourth, stn1 mutants accumulate single-stranded DNA at non-telomeric genome locations, imposing a requirement for post-replication DNA repair. We discuss these interactions in terms of a model in which Stn1 acts as an accessory replication factor that facilitates MCM activation at ORIs and potentially also maintains MCM activity at replication forks advancing through challenging templates.
期刊介绍:
Current Genetics publishes genetic, genomic, molecular and systems-level analysis of eukaryotic and prokaryotic microorganisms and cell organelles. All articles are peer-reviewed. The journal welcomes submissions employing any type of research approach, be it analytical (aiming at a better understanding), applied (aiming at practical applications), synthetic or theoretical.
Current Genetics no longer accepts manuscripts describing the genome sequence of mitochondria/chloroplast of a small number of species. Manuscripts covering sequence comparisons and analyses that include a large number of species will still be considered.