首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Sequential steps in DNA replication are inhibited to ensure reduction of ploidy in meiosis
Authors:Hui Hua  Mandana Namdar  Olivier Ganier  Juraj Gregan  Marcel Méchali  Stephen E Kearsey
Institution:University of North Carolina;aDepartment of Zoology, University of Oxford, Oxford OX1 3PS, United Kingdom;bInstitut de Génétique Humaine, Centre National de la Recherche Scientifique, Réplication et Dynamique du Génome, 34396 Montpellier Cedex 5, France;cMax F. Perutz Laboratories, 1030 Vienna, Austria;dDepartment of Genetics, Comenius University, Bratislava, Slovakia
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.
Keywords:
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号