Probing Enhanced Double-Strand Break Formation at Abasic Sites within Clustered Lesions in Nucleosome Core Particles.

摘要: DNA is rapidly cleaved under mild alkaline conditions at apyrimidinic/apurinic sites, but the half-life several weeks in phosphate buffer (pH 7.5). However, abasic sites are ∼100-fold more reactive within nucleosome core particles (NCPs). Histone proteins catalyze strand scission, and superhelical location 1.5, histone H4 tail largely responsible for accelerated cleavage. The rate constant scission an site enhanced further a particle when it part of bistranded lesion containing proximal break. Cleavage this form results highly deleterious double-strand This acceleration dependent upon position NCP its structure. enhancement cleavage apurinic/apyrimidinic drops off as distance between break increases negligible once two forms damage separated by 7 bp. double-...