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Replication factory activation can be decoupled from the replication timing program by modulating Cdk levels

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Replication factory activation can be decoupled from the replication timing program by modulating Cdk levels. / Thomson, Alexander M.; Gillespie, Peter J.; Blow, J. Julian (Lead / Corresponding author).

In: Journal of Cell Biology, Vol. 188, No. 2, 25.01.2010, p. 209-221.

Research output: Contribution to journalArticle

Harvard

Thomson, AM, Gillespie, PJ & Blow, JJ 2010, 'Replication factory activation can be decoupled from the replication timing program by modulating Cdk levels' Journal of Cell Biology, vol 188, no. 2, pp. 209-221., 10.1083/jcb.200911037

APA

Thomson, A. M., Gillespie, P. J., & Blow, J. J. (2010). Replication factory activation can be decoupled from the replication timing program by modulating Cdk levels. Journal of Cell Biology, 188(2), 209-221. 10.1083/jcb.200911037

Vancouver

Thomson AM, Gillespie PJ, Blow JJ. Replication factory activation can be decoupled from the replication timing program by modulating Cdk levels. Journal of Cell Biology. 2010 Jan 25;188(2):209-221. Available from: 10.1083/jcb.200911037

Author

Thomson, Alexander M.; Gillespie, Peter J.; Blow, J. Julian (Lead / Corresponding author) / Replication factory activation can be decoupled from the replication timing program by modulating Cdk levels.

In: Journal of Cell Biology, Vol. 188, No. 2, 25.01.2010, p. 209-221.

Research output: Contribution to journalArticle

Bibtex - Download

@article{e336b74174754fefbae8b2a6e8725e75,
title = "Replication factory activation can be decoupled from the replication timing program by modulating Cdk levels",
keywords = "CYCLIN-DEPENDENT KINASES, XENOPUS EGG EXTRACTS, S-PHASE CHECKPOINT, DNA-REPLICATION, CELL-CYCLE, DORMANT ORIGINS, BUDDING YEAST, FISSION YEAST, CHROMOSOMAL DOMAINS, REPLICON CLUSTERS",
author = "Thomson, {Alexander M.} and Gillespie, {Peter J.} and Blow, {J. Julian}",
year = "2010",
doi = "10.1083/jcb.200911037",
volume = "188",
number = "2",
pages = "209--221",
journal = "Journal of Cell Biology",
issn = "0021-9525",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Replication factory activation can be decoupled from the replication timing program by modulating Cdk levels

A1 - Thomson,Alexander M.

A1 - Gillespie,Peter J.

A1 - Blow,J. Julian

AU - Thomson,Alexander M.

AU - Gillespie,Peter J.

AU - Blow,J. Julian

PY - 2010/1/25

Y1 - 2010/1/25

N2 - <p>In the metazoan replication timing program, clusters of replication origins located in different subchromosomal domains fire at different times during S phase. We have used Xenopus laevis egg extracts to drive an accelerated replication timing program in mammalian nuclei. Although replicative stress caused checkpoint-induced slowing of the timing program, inhibition of checkpoint kinases in an unperturbed S phase did not accelerate it. Lowering cyclin-dependent kinase (Cdk) activity slowed both replication rate and progression through the timing program, whereas raising Cdk activity increased them. Surprisingly, modest alteration of Cdk activity changed the amount of DNA synthesized during different stages of the timing program. This was associated with a change in the number of active replication factories, whereas the distribution of origins within active factories remained relatively normal. The ability of Cdks to differentially effect replication initiation, factory activation, and progression through the timing program provides new insights into the way that chromosomal DNA replication is organized during S phase.</p>

AB - <p>In the metazoan replication timing program, clusters of replication origins located in different subchromosomal domains fire at different times during S phase. We have used Xenopus laevis egg extracts to drive an accelerated replication timing program in mammalian nuclei. Although replicative stress caused checkpoint-induced slowing of the timing program, inhibition of checkpoint kinases in an unperturbed S phase did not accelerate it. Lowering cyclin-dependent kinase (Cdk) activity slowed both replication rate and progression through the timing program, whereas raising Cdk activity increased them. Surprisingly, modest alteration of Cdk activity changed the amount of DNA synthesized during different stages of the timing program. This was associated with a change in the number of active replication factories, whereas the distribution of origins within active factories remained relatively normal. The ability of Cdks to differentially effect replication initiation, factory activation, and progression through the timing program provides new insights into the way that chromosomal DNA replication is organized during S phase.</p>

KW - CYCLIN-DEPENDENT KINASES

KW - XENOPUS EGG EXTRACTS

KW - S-PHASE CHECKPOINT

KW - DNA-REPLICATION

KW - CELL-CYCLE

KW - DORMANT ORIGINS

KW - BUDDING YEAST

KW - FISSION YEAST

KW - CHROMOSOMAL DOMAINS

KW - REPLICON CLUSTERS

UR - http://www.scopus.com/inward/record.url?scp=76149140088&partnerID=8YFLogxK

U2 - 10.1083/jcb.200911037

DO - 10.1083/jcb.200911037

M1 - Article

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 2

VL - 188

SP - 209

EP - 221

ER -

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