Rapid Histone-Catalyzed DNA Lesion Excision and Accompanying Protein Modification in Nucleosomes and Nucleosome Core Particles

摘要: C5′-Hydrogen atoms are frequently abstracted during DNA oxidation. The oxidized abasic lesion 5′-(2-phosphoryl-1,4-dioxobutane) (DOB) is an electrophilic product of the C5′-radical. DOB a potent irreversible inhibitor polymerase β, and forms interstrand cross-links in free DNA. We examined reactivity within nucleosomes nucleosome core particles (NCPs), monomeric component chromatin. Depending upon position at which generated NCP, it excised from nucleosomal rate 275–1500-fold faster than that half-life (7.0–16.8 min) NCPs shorter any other lesion. DOB’s lifetime also significantly estimated site cell, suggesting observed chemistry would occur intracellularly. Histones catalyze excision when present linker region nucleosome. Schiff-base formation between histone proteins detected nuc...