Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

APE1 (Ref-1) is an essential human protein involved in DNA damage repair and regulation of transcription. Although the cellular functions and biochemical properties of APE1 are well characterized, the mechanism involved in regulation of the cellular levels of this important DNA repair/transcriptional regulation enzyme, remains poorly understood. Using an in vitro ubiquitylation assay, we have now purified the human E3 ubiquitin ligase UBR3 as a major activity that polyubiquitylates APE1 at multiple lysine residues clustered on the N-terminal tail. We further show that a knockout of the Ubr3 gene in mouse embryonic fibroblasts leads to an up-regulation of the cellular levels of APE1 protein and subsequent genomic instability. These data propose an important role for UBR3 in the control of the steady state levels of APE1 and consequently error free DNA repair.

Original publication

DOI

10.1093/nar/gkr744

Type

Journal article

Journal

Nucleic Acids Res

Publication Date

01/2012

Volume

40

Pages

701 - 711

Keywords

Animals, DNA-(Apurinic or Apyrimidinic Site) Lyase, Gene Knockout Techniques, Genomic Instability, HeLa Cells, Humans, Lysine, Mice, Ubiquitin-Protein Ligases, Ubiquitination