1. Sequential post-translational modifications regulate damaged DNA-binding protein DDB2 function.
- Author
-
Kaneoka, Hidenori, Arakawa, Kazuhiko, Masuda, Yusuke, Ogawa, Daiki, Sugimoto, Kota, Fukata, Risako, Tsuge-Shoji, Maasa, Nishijima, Ken-ichi, and Iijima, Shinji
- Subjects
DNA repair ,EXCISION repair ,POST-translational modification ,DNA-binding proteins ,XERODERMA pigmentosum - Abstract
Nucleotide excision repair (NER) is a major DNA repair system and hereditary defects in this system cause critical genetic diseases (e.g. xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy). Various proteins are involved in the eukaryotic NER system and undergo several post-translational modifications. Damaged DNA-binding protein 2 (DDB2) is a DNA damage recognition factor in the NER pathway. We previously demonstrated that DDB2 was SUMOylated in response to UV irradiation; however, its physiological roles remain unclear. We herein analysed several mutants and showed that the N-terminal tail of DDB2 was the target for SUMOylation; however, this region did not contain a consensus SUMOylation sequence. We found a SUMO-interacting motif (SIM) in the N-terminal tail that facilitated SUMOylation. The ubiquitination of a SUMOylation-deficient DDB2 SIM mutant was decreased, and its retention of chromatin was prolonged. The SIM mutant showed impaired NER, possibly due to a decline in the timely handover of the lesion site to XP complementation group C. These results suggest that the SUMOylation of DDB2 facilitates NER through enhancements in ubiquitination. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF