A kinase-independent function of c-Abl in promoting proteolytic destruction of damaged DNA binding proteins. Academic Article uri icon

Overview

abstract

  • Damaged DNA binding proteins (DDBs) play a critical role in the initial recognition of UV-damaged DNA and mediate recruitment of nucleotide excision repair factors. Previous studies identified DDB2 as a target of the CUL-4A ubiquitin ligase. However, the biochemical mechanism governing DDB proteolysis and its underlying physiological function in the removal of UV-induced DNA damage are largely unknown. Here, we report that the c-Abl nonreceptor tyrosine kinase negatively regulates the repair of UV-induced photolesions on genomic DNA. Biochemical studies revealed that c-Abl promotes CUL-4A-mediated DDB ubiquitination and degradation in a manner that does not require its tyrosine kinase activity both under normal growth conditions and following UV irradiation. Moreover, c-Abl activates DDB degradation in part by alleviating the inhibitory effect of CAND1/TIP120A on CUL-4A. These results revealed a kinase-independent function of c-Abl in a ubiquitin-proteolytic pathway that regulates the damage recognition step of nucleotide excision repair.

publication date

  • May 19, 2006

Research

keywords

  • DNA Damage
  • DNA Repair
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins c-abl

Identity

Scopus Document Identifier

  • 33646685947

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2006.04.021

PubMed ID

  • 16713579

Additional Document Info

volume

  • 22

issue

  • 4