title: Sequential steps in DNA replication are inhibited to ensure reduction of ploidy in meiosis.
abstract: Meiosis involves two successive rounds of chromosome segregation without an intervening S phase. Exit from meiosis I is distinct from mitotic exit, in that replication origins are not licensed by Mcm2-7 chromatin binding, but spindle disassembly occurs during a transient interphase-like state before meiosis II. The absence of licensing is assumed to explain the block to DNA replication, but this has not been formally tested. Here we attempt to subvert this block by expressing the licensing control factors Cdc18 and Cdt1 during the interval between meiotic nuclear divisions. Surprisingly, this leads only to a partial round of DNA replication, even when these factors are overexpressed and effect clear Mcm2-7 chromatin binding. Combining Cdc18 and Cdt1 expression with modulation of cyclin-dependent kinase activity, activation of Dbf4-dependent kinase, or deletion of the Spd1 inhibitor of ribonucleotide reductase has little additional effect on the extent of DNA replication. Single-molecule analysis indicates this partial round of replication results from inefficient progression of replication forks, and thus both initiation and elongation replication steps may be inhibited in late meiosis. In addition, DNA replication or damage during the meiosis I-II interval fails to arrest meiotic progress, suggesting absence of checkpoint regulation of meiosis II entry.
authors.affiliation: Department of Zoology, University of Oxford, Oxford OX1 3PS, United Kingdom.
authors.forename: Hui
authors.initials: H
authors.lastname: Hua
authors.forename: Mandana
authors.initials: M
authors.lastname: Namdar
authors.forename: Olivier
authors.initials: O
authors.lastname: Ganier
authors.forename: Juraj
authors.initials: J
authors.lastname: Gregan
authors.forename: Marcel
authors.initials: M
authors.lastname: Méchali
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Kearsey
mesh_terms: D002843:Chromatin / Q000235:genetics / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone; D020090:Chromosome Segregation / Q000235:genetics; D004261:DNA Replication / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D008540:Meiosis / Q000235:genetics*; D010766:Phosphorylation; D011003:Ploidies; D016196:S Phase / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C069199:MCM2 protein, S cerevisiae