CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis. / Mailand, Niels; Diffley, John F X.

In: Cell, Vol. 122, No. 6, 23.09.2005, p. 915-26.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Mailand, N & Diffley, JFX 2005, 'CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis', Cell, vol. 122, no. 6, pp. 915-26. https://doi.org/10.1016/j.cell.2005.08.013

APA

Mailand, N., & Diffley, J. F. X. (2005). CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis. Cell, 122(6), 915-26. https://doi.org/10.1016/j.cell.2005.08.013

Vancouver

Mailand N, Diffley JFX. CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis. Cell. 2005 Sep 23;122(6):915-26. https://doi.org/10.1016/j.cell.2005.08.013

Author

Mailand, Niels ; Diffley, John F X. / CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis. In: Cell. 2005 ; Vol. 122, No. 6. pp. 915-26.

Bibtex

@article{9f2d63d74b964188840b0a8c64eac403,
title = "CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis",
abstract = "Cyclin-dependent kinases (CDKs) restrict DNA replication origin firing to once per cell cycle by preventing the assembly of prereplicative complexes (pre-RCs; licensing) outside of G1 phase. Paradoxically, under certain circumstances, CDKs such as cyclin E-cdk2 are also required to promote licensing. Here, we show that CDK phosphorylation of the essential licensing factor Cdc6 stabilizes it by preventing its association with the anaphase promoting complex/cyclosome (APC/C). APC/C-dependent Cdc6 proteolysis prevents pre-RC assembly in quiescent cells and, when cells reenter the cell cycle from quiescence, CDK-dependent Cdc6 stabilization allows Cdc6 to accumulate before the licensing inhibitors geminin and cyclin A which are also APC/C substrates. This novel mechanism for regulating protein stability establishes a window of time prior to S phase when pre-RCs can assemble which we propose represents a critical function of cyclin E.",
keywords = "Anaphase-Promoting Complex-Cyclosome, Cell Cycle, Cell Cycle Proteins, Cell Line, Tumor, Cyclin-Dependent Kinases, DNA Replication, Humans, Nuclear Proteins, Phosphorylation, Replication Origin, S Phase, Ubiquitin-Protein Ligase Complexes",
author = "Niels Mailand and Diffley, {John F X}",
year = "2005",
month = sep,
day = "23",
doi = "10.1016/j.cell.2005.08.013",
language = "English",
volume = "122",
pages = "915--26",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "6",

}

RIS

TY - JOUR

T1 - CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis

AU - Mailand, Niels

AU - Diffley, John F X

PY - 2005/9/23

Y1 - 2005/9/23

N2 - Cyclin-dependent kinases (CDKs) restrict DNA replication origin firing to once per cell cycle by preventing the assembly of prereplicative complexes (pre-RCs; licensing) outside of G1 phase. Paradoxically, under certain circumstances, CDKs such as cyclin E-cdk2 are also required to promote licensing. Here, we show that CDK phosphorylation of the essential licensing factor Cdc6 stabilizes it by preventing its association with the anaphase promoting complex/cyclosome (APC/C). APC/C-dependent Cdc6 proteolysis prevents pre-RC assembly in quiescent cells and, when cells reenter the cell cycle from quiescence, CDK-dependent Cdc6 stabilization allows Cdc6 to accumulate before the licensing inhibitors geminin and cyclin A which are also APC/C substrates. This novel mechanism for regulating protein stability establishes a window of time prior to S phase when pre-RCs can assemble which we propose represents a critical function of cyclin E.

AB - Cyclin-dependent kinases (CDKs) restrict DNA replication origin firing to once per cell cycle by preventing the assembly of prereplicative complexes (pre-RCs; licensing) outside of G1 phase. Paradoxically, under certain circumstances, CDKs such as cyclin E-cdk2 are also required to promote licensing. Here, we show that CDK phosphorylation of the essential licensing factor Cdc6 stabilizes it by preventing its association with the anaphase promoting complex/cyclosome (APC/C). APC/C-dependent Cdc6 proteolysis prevents pre-RC assembly in quiescent cells and, when cells reenter the cell cycle from quiescence, CDK-dependent Cdc6 stabilization allows Cdc6 to accumulate before the licensing inhibitors geminin and cyclin A which are also APC/C substrates. This novel mechanism for regulating protein stability establishes a window of time prior to S phase when pre-RCs can assemble which we propose represents a critical function of cyclin E.

KW - Anaphase-Promoting Complex-Cyclosome

KW - Cell Cycle

KW - Cell Cycle Proteins

KW - Cell Line, Tumor

KW - Cyclin-Dependent Kinases

KW - DNA Replication

KW - Humans

KW - Nuclear Proteins

KW - Phosphorylation

KW - Replication Origin

KW - S Phase

KW - Ubiquitin-Protein Ligase Complexes

U2 - 10.1016/j.cell.2005.08.013

DO - 10.1016/j.cell.2005.08.013

M3 - Journal article

C2 - 16153703

VL - 122

SP - 915

EP - 926

JO - Cell

JF - Cell

SN - 0092-8674

IS - 6

ER -

ID: 124903650