title: Managing Single-Stranded DNA during Replication Stress in Fission Yeast.
abstract: Replication fork stalling generates a variety of responses, most of which cause an increase in single-stranded DNA. ssDNA is a primary signal of replication distress that activates cellular checkpoints. It is also a potential source of genome instability and a substrate for mutation and recombination. Therefore, managing ssDNA levels is crucial to chromosome integrity. Limited ssDNA accumulation occurs in wild-type cells under stress. In contrast, cells lacking the replication checkpoint cannot arrest forks properly and accumulate large amounts of ssDNA. This likely occurs when the replication fork polymerase and helicase units are uncoupled. Some cells with mutations in the replication helicase (mcm-ts) mimic checkpoint-deficient cells, and accumulate extensive areas of ssDNA to trigger the G2-checkpoint. Another category of helicase mutant (mcm4-degron) causes fork stalling in early S-phase due to immediate loss of helicase function. Intriguingly, cells realize that ssDNA is present, but fail to detect that they accumulate ssDNA, and continue to divide. Thus, the cellular response to replication stalling depends on checkpoint activity and the time that replication stress occurs in S-phase. In this review we describe the signs, signals, and symptoms of replication arrest from an ssDNA perspective. We explore the possible mechanisms for these effects. We also advise the need for caution when detecting and interpreting data related to the accumulation of ssDNA.
authors.affiliation: Department of Chemistry and Biology, Ryerson University, 350 Victoria Street Toronto, ON M5B 2K3, Canada. ssabatinos@ryerson.ca.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Sabatinos
authors.affiliation: Program in Molecular and Computational Biology, University of Southern California, 1050 Childs Way, Los Angeles, CA 90089, USA. Forsburg@usc.edu.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Forsburg
mesh_terms: D004249:DNA Damage; D004261:DNA Replication; D004271:DNA, Fungal; D004277:DNA, Single-Stranded; D006801:Humans; D012568:Schizosaccharomyces / Q000235:genetics*
chemical_list: D004271:DNA, Fungal; D004277:DNA, Single-Stranded
keywords: DNA replication; MCM; RPA; Schizosaccharomyces pombe; checkpoint; genome stability; helicase; replication stress; single-stranded DNA