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...

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Main Authors: Hua, H, Namdar, M, Ganier, O, Gregan, J, Méchali, M, Kearsey, S
Format: Journal article
Language:English
Published: 2013
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author Hua, H
Namdar, M
Ganier, O
Gregan, J
Méchali, M
Kearsey, S
author_facet Hua, H
Namdar, M
Ganier, O
Gregan, J
Méchali, M
Kearsey, S
author_sort Hua, H
collection OXFORD
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.
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spelling oxford-uuid:9088aeaa-0724-4543-a544-643ebee0d7ab2022-03-26T23:12:17ZSequential steps in DNA replication are inhibited to ensure reduction of ploidy in meiosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9088aeaa-0724-4543-a544-643ebee0d7abEnglishSymplectic Elements at Oxford2013Hua, HNamdar, MGanier, OGregan, JMéchali, MKearsey, SMeiosis 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.
spellingShingle Hua, H
Namdar, M
Ganier, O
Gregan, J
Méchali, M
Kearsey, S
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
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AT greganj sequentialstepsindnareplicationareinhibitedtoensurereductionofploidyinmeiosis
AT mechalim sequentialstepsindnareplicationareinhibitedtoensurereductionofploidyinmeiosis
AT kearseys sequentialstepsindnareplicationareinhibitedtoensurereductionofploidyinmeiosis