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Dynamic interactions of high Cdt1 and geminin levels regulate S phase in early Xenopus embryos

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Dynamic interactions of high Cdt1 and geminin levels regulate S phase in early Xenopus embryos. / Kisielewska, Jolanta; Blow, J. Julian.

In: Development, Vol. 139, No. 1, 01.01.2012, p. 63-74.

Research output: Contribution to journalArticle

Harvard

Kisielewska, J & Blow, JJ 2012, 'Dynamic interactions of high Cdt1 and geminin levels regulate S phase in early Xenopus embryos' Development, vol 139, no. 1, pp. 63-74.

APA

Kisielewska, J., & Blow, J. J. (2012). Dynamic interactions of high Cdt1 and geminin levels regulate S phase in early Xenopus embryos. Development, 139(1), 63-74doi: 10.1242/dev.068676

Vancouver

Kisielewska J, Blow JJ. Dynamic interactions of high Cdt1 and geminin levels regulate S phase in early Xenopus embryos. Development. 2012 Jan 1;139(1):63-74.

Author

Kisielewska, Jolanta; Blow, J. Julian / Dynamic interactions of high Cdt1 and geminin levels regulate S phase in early Xenopus embryos.

In: Development, Vol. 139, No. 1, 01.01.2012, p. 63-74.

Research output: Contribution to journalArticle

Bibtex - Download

@article{89b8c6b854e243f69dc96a295c9a7782,
title = "Dynamic interactions of high Cdt1 and geminin levels regulate S phase in early Xenopus embryos",
author = "Jolanta Kisielewska and Blow, {J. Julian}",
year = "2012",
volume = "139",
number = "1",
pages = "63--74",
journal = "Development",
issn = "0950-1991",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Dynamic interactions of high Cdt1 and geminin levels regulate S phase in early Xenopus embryos

A1 - Kisielewska,Jolanta

A1 - Blow,J. Julian

AU - Kisielewska,Jolanta

AU - Blow,J. Julian

PY - 2012/1/1

Y1 - 2012/1/1

N2 - <p>Cdt1 plays a key role in licensing DNA for replication. In the somatic cells of metazoans, both Cdt1 and its natural inhibitor geminin show reciprocal fluctuations in their protein levels owing to cell cycle-dependent proteolysis. Here, we show that the protein levels of Cdt1 and geminin are persistently high during the rapid cell cycles of the early Xenopus embryo. Immunoprecipitation of Cdt1 and geminin complexes, together with their cell cycle spatiotemporal dynamics, strongly supports the hypothesis that Cdt1 licensing activity is regulated by periodic interaction with geminin rather than its proteolysis. Overexpression of ectopic geminin slows down, but neither arrests early embryonic cell cycles nor affects endogenous geminin levels; apparent embryonic lethality is observed around 3-4 hours after mid-blastula transition. However, functional knockdown of geminin by Delta Cdt1_193-447, which lacks licensing activity and degradation sequences, causes cell cycle arrest and DNA damage in affected cells. This contributes to subsequent developmental defects in treated embryos. Our results clearly show that rapidly proliferating early Xenopus embryonic cells are able to regulate replication licensing in the persistent presence of high levels of licensing proteins by relying on changing interactions between Cdt1 and geminin during the cell cycle, but not their degradation.</p>

AB - <p>Cdt1 plays a key role in licensing DNA for replication. In the somatic cells of metazoans, both Cdt1 and its natural inhibitor geminin show reciprocal fluctuations in their protein levels owing to cell cycle-dependent proteolysis. Here, we show that the protein levels of Cdt1 and geminin are persistently high during the rapid cell cycles of the early Xenopus embryo. Immunoprecipitation of Cdt1 and geminin complexes, together with their cell cycle spatiotemporal dynamics, strongly supports the hypothesis that Cdt1 licensing activity is regulated by periodic interaction with geminin rather than its proteolysis. Overexpression of ectopic geminin slows down, but neither arrests early embryonic cell cycles nor affects endogenous geminin levels; apparent embryonic lethality is observed around 3-4 hours after mid-blastula transition. However, functional knockdown of geminin by Delta Cdt1_193-447, which lacks licensing activity and degradation sequences, causes cell cycle arrest and DNA damage in affected cells. This contributes to subsequent developmental defects in treated embryos. Our results clearly show that rapidly proliferating early Xenopus embryonic cells are able to regulate replication licensing in the persistent presence of high levels of licensing proteins by relying on changing interactions between Cdt1 and geminin during the cell cycle, but not their degradation.</p>

KW - Cdt1:Geminin

KW - DNA replication

KW - Xenopus embryos

KW - ORIGIN RECOGNITION COMPLEX

KW - EUKARYOTIC DNA-REPLICATION

KW - CELL-CYCLE

KW - PREVENTS REREPLICATION

KW - RE-REPLICATION

KW - NUCLEAR IMPORT

KW - LICENSING FACTOR

KW - DOWN-REGULATION

KW - EGG EXTRACTS

KW - EXPRESSION

U2 - 10.1242/dev.068676

DO - 10.1242/dev.068676

M1 - Article

JO - Development

JF - Development

SN - 0950-1991

IS - 1

VL - 139

SP - 63

EP - 74

ER -

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