Journal
NUCLEIC ACIDS RESEARCH
Volume 39, Issue 8, Pages 3156-3165Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkq1142
Keywords
-
Categories
Funding
- G. Harold and Leila Y. Mathers Charitable Foundation
- Aid for Cancer Research
- Northeastern University
- National Natural Science Foundation of China [30700607]
- National Institutes of Health [RO1 AI065639]
- Cancer Research Institute fellowship
Ask authors/readers for more resources
DNA repair is required to maintain genome stability in stem cells and early embryos. At critical junctures, oxidative damage to DNA requires the base excision repair (BER) pathway. Since early zebrafish embryos lack the major polymerase in BER, DNA polymerase ss, repair proceeds via replicative polymerases, even though there is ample polb mRNA. Here, we report that Polb protein fails to appear at the appropriate time in development when AP endonuclease 1 (Apex), the upstream protein in BER, is knocked down. Because polb contains a Creb1 binding site, we examined whether knockdown of Apex affects creb1. Apex knockdown results in loss of Creb1 and Creb complex members but not Creb1 phosphorylation. This effect is independent of p53. Although both apex and creb1 mRNA rescue Creb1 and Polb after Apex knockdown, Apex is not a co-activator of creb1 transcription. This observation has broad significance, as similar results occur when Apex is inhibited in B cells from apex(+/-) mice. These results describe a novel regulatory circuit involving Apex, Creb1 and Polb and provide a mechanism for lethality of Apex loss in higher eukaryotes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available