Global Repair Profile of Human Alkyladenine DNA Glycosylase on Nucleosomes Reveals DNA Packaging Effects.

ABSTRACT: Alkyladenine DNA glycosylase (AAG) is the only known human glycosylase capable of excising alkylated purines from DNA, including the highly mutagenic 1,N⁶-ethenoadenine (εA) lesion. Here, we examine the ability of AAG to excise εA from a nucleosome core particle (NCP), which is the primary repeating unit of DNA packaging in eukaryotes. Using chemical synthesis techniques, we assembled a global population of NCPs in which A is replaced with εA. While each NCP contains no more than one εA lesion, the total population contains εA in 49 distinct geometric positions. Using this global εA-containing NCP system, we obtained kinetic parameters of AAG throughout the NCP architecture. We observed monophasic reaction kinetics across the NCP, but varying amounts of AAG excision. AAG

SUBMITTER: Kennedy EE 

PROVIDER: S-EPMC6697574 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature