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Re-replication induced by geminin depletion occurs from G2 and is enhanced by checkpoint activation

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Re-replication induced by geminin depletion occurs from G2 and is enhanced by checkpoint activation. / Klotz-Noack, Kathleen; McIntosh, Debbie; Schurch, Nicholas; Pratt, Norman; Blow, J. Julian.

In: Journal of Cell Science, Vol. 125, No. 10, 15.05.2012, p. 2436-2445.

Research output: Contribution to journalArticle

Harvard

Klotz-Noack, K, McIntosh, D, Schurch, N, Pratt, N & Blow, JJ 2012, 'Re-replication induced by geminin depletion occurs from G2 and is enhanced by checkpoint activation' Journal of Cell Science, vol 125, no. 10, pp. 2436-2445., 10.1242/jcs.100883

APA

Klotz-Noack, K., McIntosh, D., Schurch, N., Pratt, N., & Blow, J. J. (2012). Re-replication induced by geminin depletion occurs from G2 and is enhanced by checkpoint activation. Journal of Cell Science, 125(10), 2436-2445. 10.1242/jcs.100883

Vancouver

Klotz-Noack K, McIntosh D, Schurch N, Pratt N, Blow JJ. Re-replication induced by geminin depletion occurs from G2 and is enhanced by checkpoint activation. Journal of Cell Science. 2012 May 15;125(10):2436-2445. Available from: 10.1242/jcs.100883

Author

Klotz-Noack, Kathleen; McIntosh, Debbie; Schurch, Nicholas; Pratt, Norman; Blow, J. Julian / Re-replication induced by geminin depletion occurs from G2 and is enhanced by checkpoint activation.

In: Journal of Cell Science, Vol. 125, No. 10, 15.05.2012, p. 2436-2445.

Research output: Contribution to journalArticle

Bibtex - Download

@article{dffa02f6d4804c23a959fbbb9f98e265,
title = "Re-replication induced by geminin depletion occurs from G2 and is enhanced by checkpoint activation",
author = "Kathleen Klotz-Noack and Debbie McIntosh and Nicholas Schurch and Norman Pratt and Blow, {J. Julian}",
year = "2012",
doi = "10.1242/jcs.100883",
volume = "125",
number = "10",
pages = "2436--2445",
journal = "Journal of Cell Science",
issn = "0021-9533",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Re-replication induced by geminin depletion occurs from G2 and is enhanced by checkpoint activation

A1 - Klotz-Noack,Kathleen

A1 - McIntosh,Debbie

A1 - Schurch,Nicholas

A1 - Pratt,Norman

A1 - Blow,J. Julian

AU - Klotz-Noack,Kathleen

AU - McIntosh,Debbie

AU - Schurch,Nicholas

AU - Pratt,Norman

AU - Blow,J. Julian

PY - 2012/5/15

Y1 - 2012/5/15

N2 - <p>To prevent re-replication of DNA in a single cell cycle, the licensing of replication origins by Mcm2-7 is prevented during S and G2 phases. Animal cells achieve this by cell-cycle-regulated proteolysis of the essential licensing factor Cdt1 and inhibition of Cdt1 by geminin. Here we investigate the consequences of ablating geminin in synchronised human U2OS cells. Following geminin loss, cells complete an apparently normal S phase, but a proportion arrest at the G2-M boundary. When Cdt1 accumulates in these cells, DNA re-replicates, suggesting that the key role of geminin is to prevent re-licensing in G2. If cell cycle checkpoints are inhibited in cells lacking geminin, cells progress through mitosis and less re-replication occurs. Checkpoint kinases thereby amplify re-replication into an all-or-nothing response by delaying geminin-depleted cells in G2. Deep DNA sequencing revealed no preferential re-replication of specific genomic regions after geminin depletion. This is consistent with the observation that cells in G2 have lost their replication timing information. By contrast, when Cdt1 is overexpressed or is stabilised by the neddylation inhibitor MLN4924, re-replication can occur throughout S phase.</p>

AB - <p>To prevent re-replication of DNA in a single cell cycle, the licensing of replication origins by Mcm2-7 is prevented during S and G2 phases. Animal cells achieve this by cell-cycle-regulated proteolysis of the essential licensing factor Cdt1 and inhibition of Cdt1 by geminin. Here we investigate the consequences of ablating geminin in synchronised human U2OS cells. Following geminin loss, cells complete an apparently normal S phase, but a proportion arrest at the G2-M boundary. When Cdt1 accumulates in these cells, DNA re-replicates, suggesting that the key role of geminin is to prevent re-licensing in G2. If cell cycle checkpoints are inhibited in cells lacking geminin, cells progress through mitosis and less re-replication occurs. Checkpoint kinases thereby amplify re-replication into an all-or-nothing response by delaying geminin-depleted cells in G2. Deep DNA sequencing revealed no preferential re-replication of specific genomic regions after geminin depletion. This is consistent with the observation that cells in G2 have lost their replication timing information. By contrast, when Cdt1 is overexpressed or is stabilised by the neddylation inhibitor MLN4924, re-replication can occur throughout S phase.</p>

U2 - 10.1242/jcs.100883

DO - 10.1242/jcs.100883

M1 - Article

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 10

VL - 125

SP - 2436

EP - 2445

ER -

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