α-N-Methylation of Damaged DNA-binding Protein 2 (DDB2) and Its Function in Nucleotide Excision Repair

• DOI: 10.1074/jbc.m114.558510
• Publication Date: 2014-04-22T02:37:02Z
• Authors: Qian Cai; Lijuan Fu; Zi Wang; Nanqin Gan; Xiaoxia Dai; Yinsheng Wang
• Keywords: DDB1

DDB2 exhibits a high affinity toward UV-damaged DNA, and it is involved in the initial steps of global genome nucleotide excision repair. Mutations gene cause genetic complementation group E xeroderma pigmentosum, an autosomal recessive disease manifested clinically by hypersensitivity to sunlight exposure increased predisposition skin cancer. Here we found that, human cells, initiating methionine residue was removed that N-terminal alanine could be methylated on its α-amino with trimethylation being major form. We also demonstrated α-N-methylation catalyzed RCC1 methyltransferase. In addition, methylation-defective mutant displayed diminished nuclear localization recruited at reduced efficiency UV-induced cyclobutane pyrimidine dimer foci. Moreover, loss this methylation conferred compromised ATM (ataxia telangiectasia mutated) activation, decreased repair, elevated sensitivity cells UV light exposure. Our study provides new knowledge about posttranslational regulation expands biological functions protein DNA