Regulators of cyclin-dependent kinases are crucial for maintaining genome integrity in S phase

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

Regulators of cyclin-dependent kinases are crucial for maintaining genome integrity in S phase. / Beck, Halfdan; Nähse, Viola; Larsen, Marie Sofie Yoo; Groth, Petra; Clancy, Trevor; Lees, Michael; Jørgensen, Mette; Helleday, Thomas; Syljuåsen, Randi G; Sørensen, Claus Storgaard.

I: Journal of Cell Biology, Bind 188, Nr. 5, 2010, s. 629-38.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Beck, H, Nähse, V, Larsen, MSY, Groth, P, Clancy, T, Lees, M, Jørgensen, M, Helleday, T, Syljuåsen, RG & Sørensen, CS 2010, 'Regulators of cyclin-dependent kinases are crucial for maintaining genome integrity in S phase', Journal of Cell Biology, bind 188, nr. 5, s. 629-38. https://doi.org/10.1083/jcb.200905059

APA

Beck, H., Nähse, V., Larsen, M. S. Y., Groth, P., Clancy, T., Lees, M., Jørgensen, M., Helleday, T., Syljuåsen, R. G., & Sørensen, C. S. (2010). Regulators of cyclin-dependent kinases are crucial for maintaining genome integrity in S phase. Journal of Cell Biology, 188(5), 629-38. https://doi.org/10.1083/jcb.200905059

Vancouver

Beck H, Nähse V, Larsen MSY, Groth P, Clancy T, Lees M o.a. Regulators of cyclin-dependent kinases are crucial for maintaining genome integrity in S phase. Journal of Cell Biology. 2010;188(5):629-38. https://doi.org/10.1083/jcb.200905059

Author

Beck, Halfdan ; Nähse, Viola ; Larsen, Marie Sofie Yoo ; Groth, Petra ; Clancy, Trevor ; Lees, Michael ; Jørgensen, Mette ; Helleday, Thomas ; Syljuåsen, Randi G ; Sørensen, Claus Storgaard. / Regulators of cyclin-dependent kinases are crucial for maintaining genome integrity in S phase. I: Journal of Cell Biology. 2010 ; Bind 188, Nr. 5. s. 629-38.

Bibtex

@article{ac493ff03cd011df928f000ea68e967b,
title = "Regulators of cyclin-dependent kinases are crucial for maintaining genome integrity in S phase",
abstract = "Maintenance of genome integrity is of critical importance to cells. To identify key regulators of genomic integrity, we screened a human cell line with a kinome small interfering RNA library. WEE1, a major regulator of mitotic entry, and CHK1 were among the genes identified. Both kinases are important negative regulators of CDK1 and -2. Strikingly, WEE1 depletion rapidly induced DNA damage in S phase in newly replicated DNA, which was accompanied by a marked increase in single-stranded DNA. This DNA damage is dependent on CDK1 and -2 as well as the replication proteins MCM2 and CDT1 but not CDC25A. Conversely, DNA damage after CHK1 inhibition is highly dependent on CDC25A. Furthermore, the inferior proliferation of CHK1-depleted cells is improved substantially by codepletion of CDC25A. We conclude that the mitotic kinase WEE1 and CHK1 jointly maintain balanced cellular control of Cdk activity during normal DNA replication, which is crucial to prevent the generation of harmful DNA lesions during replication.",
author = "Halfdan Beck and Viola N{\"a}hse and Larsen, {Marie Sofie Yoo} and Petra Groth and Trevor Clancy and Michael Lees and Mette J{\o}rgensen and Thomas Helleday and Sylju{\aa}sen, {Randi G} and S{\o}rensen, {Claus Storgaard}",
year = "2010",
doi = "10.1083/jcb.200905059",
language = "English",
volume = "188",
pages = "629--38",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "5",

}

RIS

TY - JOUR

T1 - Regulators of cyclin-dependent kinases are crucial for maintaining genome integrity in S phase

AU - Beck, Halfdan

AU - Nähse, Viola

AU - Larsen, Marie Sofie Yoo

AU - Groth, Petra

AU - Clancy, Trevor

AU - Lees, Michael

AU - Jørgensen, Mette

AU - Helleday, Thomas

AU - Syljuåsen, Randi G

AU - Sørensen, Claus Storgaard

PY - 2010

Y1 - 2010

N2 - Maintenance of genome integrity is of critical importance to cells. To identify key regulators of genomic integrity, we screened a human cell line with a kinome small interfering RNA library. WEE1, a major regulator of mitotic entry, and CHK1 were among the genes identified. Both kinases are important negative regulators of CDK1 and -2. Strikingly, WEE1 depletion rapidly induced DNA damage in S phase in newly replicated DNA, which was accompanied by a marked increase in single-stranded DNA. This DNA damage is dependent on CDK1 and -2 as well as the replication proteins MCM2 and CDT1 but not CDC25A. Conversely, DNA damage after CHK1 inhibition is highly dependent on CDC25A. Furthermore, the inferior proliferation of CHK1-depleted cells is improved substantially by codepletion of CDC25A. We conclude that the mitotic kinase WEE1 and CHK1 jointly maintain balanced cellular control of Cdk activity during normal DNA replication, which is crucial to prevent the generation of harmful DNA lesions during replication.

AB - Maintenance of genome integrity is of critical importance to cells. To identify key regulators of genomic integrity, we screened a human cell line with a kinome small interfering RNA library. WEE1, a major regulator of mitotic entry, and CHK1 were among the genes identified. Both kinases are important negative regulators of CDK1 and -2. Strikingly, WEE1 depletion rapidly induced DNA damage in S phase in newly replicated DNA, which was accompanied by a marked increase in single-stranded DNA. This DNA damage is dependent on CDK1 and -2 as well as the replication proteins MCM2 and CDT1 but not CDC25A. Conversely, DNA damage after CHK1 inhibition is highly dependent on CDC25A. Furthermore, the inferior proliferation of CHK1-depleted cells is improved substantially by codepletion of CDC25A. We conclude that the mitotic kinase WEE1 and CHK1 jointly maintain balanced cellular control of Cdk activity during normal DNA replication, which is crucial to prevent the generation of harmful DNA lesions during replication.

U2 - 10.1083/jcb.200905059

DO - 10.1083/jcb.200905059

M3 - Journal article

C2 - 20194642

VL - 188

SP - 629

EP - 638

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 5

ER -

ID: 18947812