Ubiquitin ligase UBR3 regulates cellular levels of the essential DNA repair protein APE1 and is required for genome stability.
Nucleic Acids Res
; 40(2): 701-11, 2012 Jan.
Article
en En
| MEDLINE
| ID: mdl-21933813
ABSTRACT
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Inestabilidad Genómica
/
ADN-(Sitio Apurínico o Apirimidínico) Liasa
/
Ubiquitina-Proteína Ligasas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2012
Tipo del documento:
Article
País de afiliación:
Reino Unido