The prion protein is critical for DNA repair and cell survival after genotoxic stress

被引：46

作者：

Bravard, Anne ^{[1
,2
,3
,4
]}

Auvre, Frederic ^{[1
,2
,3
,4
]}

Fantini, Damiano ^{[1
,2
,3
,4
]}

Bernardino-Sgherri, Jacqueline ^{[1
,2
,3
,4
]}

Sissoeff, Ludmilla ^{[5
]}

Daynac, Mathieu ^{[1
,2
,3
,4
]}

Xu, Zhou ^{[5
]}

Etienne, Olivier ^{[1
,2
,3
,4
]}

Dehen, Capucine ^{[5
]}

Comoy, Emmanuel ^{[5
]}

Boussin, Francois D. ^{[1
,2
,3
,4
]}

Tell, Gianluca ^{[6
]}

Deslys, Jean-Philippe ^{[5
]}

Radicella, J. Pablo ^{[1
,2
,3
,4
]}

机构：

[1] CEA, Inst Cellular & Mol Radiobiol, F-92265 Fontenay Aux Roses, France

[2] INSERM, U967, F-92265 Fontenay Aux Roses, France

[3] Univ Paris Diderot, UMR 967, F-92265 Fontenay Aux Roses, France

[4] Univ Paris 11, UMR 967, F-92265 Fontenay Aux Roses, France

[5] CEA, Inst Malad Emergentes & Therapies Innovantes, Serv Etudes Prions & Infect Atyp, F-92265 Fontenay Aux Roses, France

[6] Univ Udine, Dept Med & Biol Sci, I-33100 Udine, Italy

来源：

NUCLEIC ACIDS RESEARCH | 2015年 / 43卷 / 02期

关键词：

NUCLEAR-LOCALIZATION SIGNALS; BASE EXCISION-REPAIR; OXIDATIVE STRESS; RETROGRADE TRANSPORT; DAMAGE; MICE; PRP; DISEASE; EXPRESSION; INCREASES;

D O I：

10.1093/nar/gku1342

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The prion protein (PrP) is highly conserved and ubiquitously expressed, suggesting that it plays an important physiological function. However, despite decades of investigation, this role remains elusive. Here, by using animal and cellular models, we unveil a key role of PrP in the DNA damage response. Exposure of neurons to a genotoxic stress activates PRNP transcription leading to an increased amount of PrP in the nucleus where it interacts with APE1, the major mammalian endonuclease essential for base excision repair, and stimulates its activity. Preventing the induction of PRNP results in accumulation of abasic sites in DNA and impairs cell survival after genotoxic treatment. Brains from Prnp(-/-) mice display a reduced APE1 activity and a defect in the repair of induced DNA damage in vivo. Thus, PrP is required to maintain genomic stability in response to genotoxic stresses.

引用

页码：904 / 916

页数：13

共 59 条

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