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Sequential steps in DNA replication are inhibited to ensure reduction of ploidy in meiosis
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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583662/ https://www.ncbi.nlm.nih.gov/pubmed/23303250 http://dx.doi.org/10.1091/mbc.E12-11-0825 |
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author | Hua, Hui Namdar, Mandana Ganier, Olivier Gregan, Juraj Méchali, Marcel Kearsey, Stephen E. |
author_facet | Hua, Hui Namdar, Mandana Ganier, Olivier Gregan, Juraj Méchali, Marcel Kearsey, Stephen E. |
author_sort | Hua, Hui |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3583662 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-35836622013-05-16 Sequential steps in DNA replication are inhibited to ensure reduction of ploidy in meiosis Hua, Hui Namdar, Mandana Ganier, Olivier Gregan, Juraj Méchali, Marcel Kearsey, Stephen E. Mol Biol Cell Articles 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. The American Society for Cell Biology 2013-03-01 /pmc/articles/PMC3583662/ /pubmed/23303250 http://dx.doi.org/10.1091/mbc.E12-11-0825 Text en © 2013 Hua et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Hua, Hui Namdar, Mandana Ganier, Olivier Gregan, Juraj Méchali, Marcel Kearsey, Stephen E. Sequential steps in DNA replication are inhibited to ensure reduction of ploidy in meiosis |
title | Sequential steps in DNA replication are inhibited to ensure reduction of ploidy in meiosis |
title_full | Sequential steps in DNA replication are inhibited to ensure reduction of ploidy in meiosis |
title_fullStr | Sequential steps in DNA replication are inhibited to ensure reduction of ploidy in meiosis |
title_full_unstemmed | Sequential steps in DNA replication are inhibited to ensure reduction of ploidy in meiosis |
title_short | Sequential steps in DNA replication are inhibited to ensure reduction of ploidy in meiosis |
title_sort | sequential steps in dna replication are inhibited to ensure reduction of ploidy in meiosis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583662/ https://www.ncbi.nlm.nih.gov/pubmed/23303250 http://dx.doi.org/10.1091/mbc.E12-11-0825 |
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