Search for DNA damage by human alkyladenine DNA glycosylase involves early intercalation by an aromatic residue.

ABSTRACT: DNA repair enzymes recognize and remove damaged bases that are embedded in the duplex. To gain access, most enzymes use nucleotide flipping, whereby the target nucleotide is rotated 180° into the active site. In human alkyladenine DNA glycosylase (AAG), the enzyme that initiates base excision repair of alkylated bases, the flipped-out nucleotide is stabilized by intercalation of the side chain of tyrosine 162 that replaces the lesion nucleobase. Previous kinetic studies provided evidence for the formation of a transient complex that precedes the stable flipped-out complex, but it is not clear how this complex differs from nonspecific complexes. We used site-directed mutagenesis and transient-kinetic approaches to investigate the timing of Tyr¹⁶² intercalation for AAG. The trypto

SUBMITTER: Hendershot JM 

PROVIDER: S-EPMC5625039 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature