title: Replication stress in early S phase generates apparent micronuclei and chromosome rearrangement in fission yeast.
abstract: DNA replication stress causes genome mutations, rearrangements, and chromosome missegregation, which are implicated in cancer. We analyze a fission yeast mutant that is unable to complete S phase due to a defective subunit of the MCM helicase. Despite underreplicated and damaged DNA, these cells evade the G2 damage checkpoint to form ultrafine bridges, fragmented centromeres, and uneven chromosome segregations that resembles micronuclei. These micronuclei retain DNA damage markers and frequently rejoin with the parent nucleus. Surviving cells show an increased rate of mutation and chromosome rearrangement. This first report of micronucleus-like segregation in a yeast replication mutant establishes underreplication as an important factor contributing to checkpoint escape, abnormal chromosome segregation, and chromosome instability.
authors.affiliation: Program in Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089 Department of Chemistry and Biology, Ryerson University, Toronto, ON M5B 2K3, Canada.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Sabatinos
authors.affiliation: Program in Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089.
authors.forename: Nimna S
authors.initials: NS
authors.lastname: Ranatunga
authors.affiliation: Program in Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089.
authors.forename: Ji-Ping
authors.initials: JP
authors.lastname: Yuan
authors.affiliation: Program in Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089.
authors.forename: Marc D
authors.initials: MD
authors.lastname: Green
authors.affiliation: Program in Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089 forsburg@usc.edu.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Forsburg
mesh_terms: D000483:Alleles; D002503:Centromere / Q000378:metabolism; D020090:Chromosome Segregation; D004261:DNA Replication / Q000502:physiology*; D015321:Gene Rearrangement; D048629:Micronuclei, Chromosome-Defective; D015162:Micronucleus Tests; D064148:Minichromosome Maintenance Complex Component 4 / Q000235:genetics*; D016196:S Phase / Q000502:physiology; D012568:Schizosaccharomyces / Q000166:cytology* / Q000235:genetics* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics*; D013312:Stress, Physiological / Q000235:genetics
chemical_list: D029702:Schizosaccharomyces pombe Proteins; D064148:Minichromosome Maintenance Complex Component 4; C078490:mcm4 protein, S pombe