A kinase-independent function of c-Abl in promoting proteolytic destruction of damaged DNA binding proteins MOLECULAR CELL Chen, X., Zhang, J., Lee, J., Lin, P. S., Ford, J. M., Zheng, N., Zhou, P. 2006; 22 (4): 489-499


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.

View details for DOI 10.1016/j.molcel.2006.04.021

View details for Web of Science ID 000237813300010

View details for PubMedID 16713579