You are here

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

TitleThe prion protein is critical for DNA repair and cell survival after genotoxic stress.
Publication TypeJournal Article
Year of Publication2015
AuthorsBravard, A, Auvré, F, Fantini, D, Bernardino-Sgherri, J, Sissoëff, L, Daynac, M, Xu, Z, Etienne, O, Dehen, C, Comoy, E, Boussin, FD, Tell, G, Deslys, J-P, J Radicella, P
JournalNucleic Acids Res
Volume43
Issue2
Pagination904-16
Date Published2015 Jan
ISSN1362-4962
KeywordsAnimals, Brain, Cell Line, Cell Nucleus, Cell Survival, DNA Repair, DNA-(Apurinic or Apyrimidinic Site) Lyase, Humans, Methyl Methanesulfonate, Mice, Mice, Inbred C57BL, Mutagens, Neurons, Prion Proteins, Prions, Transcriptional Activation
Abstract

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.

DOI10.1093/nar/gku1342
Alternate JournalNucleic Acids Res.
PubMed ID25539913
PubMed Central IDPMC4333392