Histone Tail Sequences Balance Their Role in Genetic Regulation and the Need to Protect DNA Against Destruction in Nucleosome Core Particles Containing Abasic Sites.

作者：Yang Kun; Greenberg Marc M

来源：ChemBioChem: a European journal of chemical biology , 2018.

DOI：10.1002/cbic.201800559

• DNA damage * nucleosomes * DNA repair * histone modification * mechanism

Abasic sites (AP) are produced 10,000 times in a single cell per day. Strand cleavage at AP is accelerated ~100-fold within a nucleosome core particle (NCP) compared to free DNA. The lysine (Lys) rich N-terminal tails of histone proteins catalyze single strand break formation via a mechanism utilized by base excision repair enzymes, despite the general dearth of Glu, Asp, and His amino acids that are typically responsible for deprotonation of Schiff base intermediates. Incorporating Glu, Asp, or His proximal to Lys residues in histone N-terminal tails increases AP reactivity as much as ~6-fold. The rate acceleration is due to more facile DNA cleavage of Schiff base intermediates. These observations raise the possibility that histone proteins may have evolved to minimize the presence of His, Glu, and Asp in their Lys rich N-terminal tails to guard against enhancing the toxic effects of DNA damage.

• 单位
  United States