WEE1 kinase protects the stability of stalled DNA replication forks by limiting CDK2 activity

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

Standard

WEE1 kinase protects the stability of stalled DNA replication forks by limiting CDK2 activity. / Elbæk, Camilla Reiter; Petrosius, Valdemaras; Benada, Jan; Erichsen, Louisa; Damgaard, Rune Busk; Sørensen, Claus Storgaard.

In: Cell Reports, Vol. 38, No. 3, 110261, 2022.

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

Harvard

Elbæk, CR, Petrosius, V, Benada, J, Erichsen, L, Damgaard, RB & Sørensen, CS 2022, 'WEE1 kinase protects the stability of stalled DNA replication forks by limiting CDK2 activity', Cell Reports, vol. 38, no. 3, 110261. https://doi.org/10.1016/j.celrep.2021.110261

APA

Elbæk, C. R., Petrosius, V., Benada, J., Erichsen, L., Damgaard, R. B., & Sørensen, C. S. (2022). WEE1 kinase protects the stability of stalled DNA replication forks by limiting CDK2 activity. Cell Reports, 38(3), [110261]. https://doi.org/10.1016/j.celrep.2021.110261

Vancouver

Elbæk CR, Petrosius V, Benada J, Erichsen L, Damgaard RB, Sørensen CS. WEE1 kinase protects the stability of stalled DNA replication forks by limiting CDK2 activity. Cell Reports. 2022;38(3). 110261. https://doi.org/10.1016/j.celrep.2021.110261

Author

Elbæk, Camilla Reiter ; Petrosius, Valdemaras ; Benada, Jan ; Erichsen, Louisa ; Damgaard, Rune Busk ; Sørensen, Claus Storgaard. / WEE1 kinase protects the stability of stalled DNA replication forks by limiting CDK2 activity. In: Cell Reports. 2022 ; Vol. 38, No. 3.

Bibtex

@article{7e445cdfd125483da36b6c7c4b209172,
title = "WEE1 kinase protects the stability of stalled DNA replication forks by limiting CDK2 activity",
abstract = "Cellular feedback systems ensure genome maintenance during DNA replication. When replication forks stall, newly replicated DNA is protected by pathways that limit excessive DNA nuclease attacks. Here we show that WEE1 activity guards against nascent DNA degradation at stalled forks. Furthermore, we identify WEE1-dependent suppression of cyclin-dependent kinase 2 (CDK2) as a major activity counteracting fork degradation. We establish DNA2 as the nuclease responsible for excessive fork degradation in WEE1-inhibited cells. In addition, WEE1 appears to be unique among CDK activity suppressors in S phase because neither CHK1 nor p21 promote fork protection as WEE1 does. Our results identify a key role of WEE1 in protecting stalled forks, which is separate from its established role in safeguarding DNA replication initiation. Our findings highlight how WEE1 inhibition evokes massive genome challenges during DNA replication, and this knowledge may improve therapeutic strategies to specifically eradicate cancer cells that frequently harbor elevated DNA replication stress.",
keywords = "cancer, CDK, cell cycle, DNA replication, fork protection, genome integrity, nucleases, replication stress, WEE1",
author = "Elb{\ae}k, {Camilla Reiter} and Valdemaras Petrosius and Jan Benada and Louisa Erichsen and Damgaard, {Rune Busk} and S{\o}rensen, {Claus Storgaard}",
note = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2022",
doi = "10.1016/j.celrep.2021.110261",
language = "English",
volume = "38",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "3",

}

RIS

TY - JOUR

T1 - WEE1 kinase protects the stability of stalled DNA replication forks by limiting CDK2 activity

AU - Elbæk, Camilla Reiter

AU - Petrosius, Valdemaras

AU - Benada, Jan

AU - Erichsen, Louisa

AU - Damgaard, Rune Busk

AU - Sørensen, Claus Storgaard

N1 - Publisher Copyright: © 2021 The Author(s)

PY - 2022

Y1 - 2022

N2 - Cellular feedback systems ensure genome maintenance during DNA replication. When replication forks stall, newly replicated DNA is protected by pathways that limit excessive DNA nuclease attacks. Here we show that WEE1 activity guards against nascent DNA degradation at stalled forks. Furthermore, we identify WEE1-dependent suppression of cyclin-dependent kinase 2 (CDK2) as a major activity counteracting fork degradation. We establish DNA2 as the nuclease responsible for excessive fork degradation in WEE1-inhibited cells. In addition, WEE1 appears to be unique among CDK activity suppressors in S phase because neither CHK1 nor p21 promote fork protection as WEE1 does. Our results identify a key role of WEE1 in protecting stalled forks, which is separate from its established role in safeguarding DNA replication initiation. Our findings highlight how WEE1 inhibition evokes massive genome challenges during DNA replication, and this knowledge may improve therapeutic strategies to specifically eradicate cancer cells that frequently harbor elevated DNA replication stress.

AB - Cellular feedback systems ensure genome maintenance during DNA replication. When replication forks stall, newly replicated DNA is protected by pathways that limit excessive DNA nuclease attacks. Here we show that WEE1 activity guards against nascent DNA degradation at stalled forks. Furthermore, we identify WEE1-dependent suppression of cyclin-dependent kinase 2 (CDK2) as a major activity counteracting fork degradation. We establish DNA2 as the nuclease responsible for excessive fork degradation in WEE1-inhibited cells. In addition, WEE1 appears to be unique among CDK activity suppressors in S phase because neither CHK1 nor p21 promote fork protection as WEE1 does. Our results identify a key role of WEE1 in protecting stalled forks, which is separate from its established role in safeguarding DNA replication initiation. Our findings highlight how WEE1 inhibition evokes massive genome challenges during DNA replication, and this knowledge may improve therapeutic strategies to specifically eradicate cancer cells that frequently harbor elevated DNA replication stress.

KW - cancer

KW - CDK

KW - cell cycle

KW - DNA replication

KW - fork protection

KW - genome integrity

KW - nucleases

KW - replication stress

KW - WEE1

U2 - 10.1016/j.celrep.2021.110261

DO - 10.1016/j.celrep.2021.110261

M3 - Journal article

C2 - 35045293

AN - SCOPUS:85122937211

VL - 38

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 3

M1 - 110261

ER -

ID: 290596575