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Histone Tail Sequences Balance Their Role in Genetic Regulation and the Need To Protect DNA against Destruction in Nucleosome Core Particles Containing Abasic Sites
Author(s) -
Yang Kun,
Greenberg Marc M.
Publication year - 2019
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800559
Subject(s) - biochemistry , nucleosome , histone , lysine , histidine , dna , chemistry , aspartic acid , ap site , glutamic acid , base excision repair , deprotonation , amino acid , dna repair , ion , organic chemistry
Abasic sites (AP) are produced 10 000 times per day in a single cell. Strand cleavage at AP is accelerated ≈100‐fold within a nucleosome core particle (NCP) compared to free DNA. The lysine‐rich N‐terminal tails of histone proteins catalyze single‐strand breaks through a mechanism used by base‐excision‐repair enzymes, despite the general dearth of glutamic acid, aspartic acid, and histidine—the amino acids that are typically responsible for deprotonation of Schiff base intermediates. Incorporating glutamic acid, aspartic acid, or histidine proximal to lysine residues in histone N‐terminal tails increases AP reactivity as much as sixfold. The rate acceleration is due to more facile DNA cleavage of Schiff‐base intermediates. These observations raise the possibility that histone proteins could have evolved to minimize the presence of histidine, glutamic acid, and aspartic acid in their lysine‐rich N‐terminal tails to guard against enhancing the toxic effects of DNA damage.