Nkx3.1 controls the DNA repair response in the mouse prostate

Hailan Zhang; Tian Zheng; Chee Wai Chua; Michael Shen; Edward P. Gelmann

doi:10.1002/pros.23131

Nkx3.1 controls the DNA repair response in the mouse prostate

Hailan Zhang, Tian Zheng, Chee Wai Chua, Michael Shen, Edward P. Gelmann

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

BACKGROUND The human prostate tumor suppressor NKX3.1 mediates the DNA repair response and interacts with the androgen receptor to assure faithful completion of transcription thereby protecting against TMPRSS2-ERG gene fusion. To determine directly the effect of Nkx3.1 in vivo we studied the DNA repair response in prostates of mice with targeted deletion of Nkx3.1. METHODS Using both drug-induced DNA damage and γ-irradiation, we assayed expression of γ-histone 2AX at time points up to 24 hr after induction of DNA damage. RESULTS We demonstrated that expression of Nkx3.1 influenced both the timing and magnitude of the DNA damage response in the prostate. CONCLUSIONS Nkx3.1 affects the DNA damage response in the murine prostate and is haploinsufficient for this phenotype.

Original language	English (US)
Pages (from-to)	402-408
Number of pages	7
Journal	Prostate
Volume	76
Issue number	4
DOIs	https://doi.org/10.1002/pros.23131
State	Published - Mar 1 2016
Externally published	Yes

Keywords

DNA repair
NKX3.1
haploinsufficiency
γhistone 2AX

ASJC Scopus subject areas

Oncology
Urology

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10.1002/pros.23131

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title = "Nkx3.1 controls the DNA repair response in the mouse prostate",

abstract = "BACKGROUND The human prostate tumor suppressor NKX3.1 mediates the DNA repair response and interacts with the androgen receptor to assure faithful completion of transcription thereby protecting against TMPRSS2-ERG gene fusion. To determine directly the effect of Nkx3.1 in vivo we studied the DNA repair response in prostates of mice with targeted deletion of Nkx3.1. METHODS Using both drug-induced DNA damage and γ-irradiation, we assayed expression of γ-histone 2AX at time points up to 24 hr after induction of DNA damage. RESULTS We demonstrated that expression of Nkx3.1 influenced both the timing and magnitude of the DNA damage response in the prostate. CONCLUSIONS Nkx3.1 affects the DNA damage response in the murine prostate and is haploinsufficient for this phenotype.",

keywords = "DNA repair, NKX3.1, haploinsufficiency, γhistone 2AX",

author = "Hailan Zhang and Tian Zheng and Chua, {Chee Wai} and Michael Shen and Gelmann, {Edward P.}",

note = "Funding Information: NCI; Grant number: P01 CA154293; CCSG; Grant number: P30 CA013696-36. Publisher Copyright: {\textcopyright} 2015 The Authors. The Prostate published by Wiley Periodicals, Inc.",

year = "2016",

month = mar,

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doi = "10.1002/pros.23131",

language = "English (US)",

volume = "76",

pages = "402--408",

journal = "Prostate",

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publisher = "John Wiley and Sons Inc.",

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TY - JOUR

T1 - Nkx3.1 controls the DNA repair response in the mouse prostate

AU - Zhang, Hailan

AU - Zheng, Tian

AU - Chua, Chee Wai

AU - Shen, Michael

AU - Gelmann, Edward P.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - BACKGROUND The human prostate tumor suppressor NKX3.1 mediates the DNA repair response and interacts with the androgen receptor to assure faithful completion of transcription thereby protecting against TMPRSS2-ERG gene fusion. To determine directly the effect of Nkx3.1 in vivo we studied the DNA repair response in prostates of mice with targeted deletion of Nkx3.1. METHODS Using both drug-induced DNA damage and γ-irradiation, we assayed expression of γ-histone 2AX at time points up to 24 hr after induction of DNA damage. RESULTS We demonstrated that expression of Nkx3.1 influenced both the timing and magnitude of the DNA damage response in the prostate. CONCLUSIONS Nkx3.1 affects the DNA damage response in the murine prostate and is haploinsufficient for this phenotype.

AB - BACKGROUND The human prostate tumor suppressor NKX3.1 mediates the DNA repair response and interacts with the androgen receptor to assure faithful completion of transcription thereby protecting against TMPRSS2-ERG gene fusion. To determine directly the effect of Nkx3.1 in vivo we studied the DNA repair response in prostates of mice with targeted deletion of Nkx3.1. METHODS Using both drug-induced DNA damage and γ-irradiation, we assayed expression of γ-histone 2AX at time points up to 24 hr after induction of DNA damage. RESULTS We demonstrated that expression of Nkx3.1 influenced both the timing and magnitude of the DNA damage response in the prostate. CONCLUSIONS Nkx3.1 affects the DNA damage response in the murine prostate and is haploinsufficient for this phenotype.

KW - DNA repair

KW - NKX3.1

KW - haploinsufficiency

KW - γhistone 2AX

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Nkx3.1 controls the DNA repair response in the mouse prostate

Abstract

Keywords

ASJC Scopus subject areas

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