Histone tails decrease N7-methyl-2'-deoxyguanosine depurination and yield DNA-protein cross-links in nucleosome core particles and cells.

ABSTRACT: Monofunctional alkylating agents preferentially react at the N7 position of 2'-deoxyguanosine in duplex DNA. Methylated DNA, such as that produced by methyl methanesulfonate (MMS) and temozolomide, exists for days in organisms. The predominant consequence of N7-methyl-2'-deoxyguanosine (MdG) is widely believed to be abasic site (AP) formation via hydrolysis, a process that is slow in free DNA. Examination of MdG reactivity within nucleosome core particles (NCPs) provided two general observations. MdG depurination rate constants are reduced in NCPs compared with when the identical DNA sequence is free in solution. The magnitude of the decrease correlates with proximity to the positively charged histone tails, and experiments in NCPs containing histone variants reveal that positively charged

SUBMITTER: Yang K 

PROVIDER: S-EPMC6275548 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature