A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance

Tobias Menzel; Viola Nähse-Kumpf; Arne Nedergaard Kousholt; Ditte Kjærsgaard Klein; Christin Lund-Andersen; Michael Lees; Jens Vilstrup Johansen; Randi G Syljuåsen; Claus Storgaard Sørensen

doi:10.1038/embor.2011.99

A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance

Tobias Menzel, Viola Nähse-Kumpf, Arne Nedergaard Kousholt, Ditte Kjærsgaard Klein, Christin Lund-Andersen, Michael Lees, Jens Vilstrup Johansen, Randi G Syljuåsen, Claus Storgaard Sørensen

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Abstract

To identify key connections between DNA-damage repair and checkpoint pathways, we performed RNA interference screens for regulators of the ionizing radiation-induced G2 checkpoint, and we identified the breast cancer gene BRCA2. The checkpoint was also abrogated following depletion of PALB2, an interaction partner of BRCA2. BRCA2 and PALB2 depletion led to premature checkpoint abrogation and earlier activation of the AURORA A-PLK1 checkpoint-recovery pathway. These results indicate that the breast cancer tumour suppressors and homologous recombination repair proteins BRCA2 and PALB2 are main regulators of G2 checkpoint maintenance following DNA-damage.

Originalsprog	Engelsk
Tidsskrift	E M B O Reports
Vol/bind	12
Udgave nummer	7
Sider (fra-til)	705-12
Antal sider	8
ISSN	1469-221X
DOI	https://doi.org/10.1038/embor.2011.99
Status	Udgivet - jul. 2011

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title = "A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance",

abstract = "To identify key connections between DNA-damage repair and checkpoint pathways, we performed RNA interference screens for regulators of the ionizing radiation-induced G2 checkpoint, and we identified the breast cancer gene BRCA2. The checkpoint was also abrogated following depletion of PALB2, an interaction partner of BRCA2. BRCA2 and PALB2 depletion led to premature checkpoint abrogation and earlier activation of the AURORA A-PLK1 checkpoint-recovery pathway. These results indicate that the breast cancer tumour suppressors and homologous recombination repair proteins BRCA2 and PALB2 are main regulators of G2 checkpoint maintenance following DNA-damage.",

author = "Tobias Menzel and Viola N{\"a}hse-Kumpf and Kousholt, {Arne Nedergaard} and Klein, {Ditte Kj{\ae}rsgaard} and Christin Lund-Andersen and Michael Lees and Johansen, {Jens Vilstrup} and Sylju{\aa}sen, {Randi G} and S{\o}rensen, {Claus Storgaard}",

year = "2011",

month = jul,

doi = "10.1038/embor.2011.99",

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T1 - A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance

AU - Menzel, Tobias

AU - Nähse-Kumpf, Viola

AU - Kousholt, Arne Nedergaard

AU - Klein, Ditte Kjærsgaard

AU - Lund-Andersen, Christin

AU - Lees, Michael

AU - Johansen, Jens Vilstrup

AU - Syljuåsen, Randi G

AU - Sørensen, Claus Storgaard

PY - 2011/7

Y1 - 2011/7

N2 - To identify key connections between DNA-damage repair and checkpoint pathways, we performed RNA interference screens for regulators of the ionizing radiation-induced G2 checkpoint, and we identified the breast cancer gene BRCA2. The checkpoint was also abrogated following depletion of PALB2, an interaction partner of BRCA2. BRCA2 and PALB2 depletion led to premature checkpoint abrogation and earlier activation of the AURORA A-PLK1 checkpoint-recovery pathway. These results indicate that the breast cancer tumour suppressors and homologous recombination repair proteins BRCA2 and PALB2 are main regulators of G2 checkpoint maintenance following DNA-damage.

AB - To identify key connections between DNA-damage repair and checkpoint pathways, we performed RNA interference screens for regulators of the ionizing radiation-induced G2 checkpoint, and we identified the breast cancer gene BRCA2. The checkpoint was also abrogated following depletion of PALB2, an interaction partner of BRCA2. BRCA2 and PALB2 depletion led to premature checkpoint abrogation and earlier activation of the AURORA A-PLK1 checkpoint-recovery pathway. These results indicate that the breast cancer tumour suppressors and homologous recombination repair proteins BRCA2 and PALB2 are main regulators of G2 checkpoint maintenance following DNA-damage.

U2 - 10.1038/embor.2011.99

DO - 10.1038/embor.2011.99

M3 - Journal article

C2 - 21637299

SN - 1469-221X

VL - 12

SP - 705

EP - 712

JO - E M B O Reports

JF - E M B O Reports

IS - 7

ER -

A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance

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