Structural Basis for Finding OG Lesions and Avoiding Undamaged G by the DNA Glycosylase MutY.

ABSTRACT: The adenine glycosylase MutY selectively initiates repair of OG:A lesions and, by comparison, avoids G:A mispairs. The ability to distinguish these closely related substrates relies on the C-terminal domain of MutY, which structurally resembles MutT. To understand the mechanism for substrate specificity, we crystallized MutY in complex with DNA containing G across from the high-affinity azaribose transition state analogue. Our structure shows that G is accommodated by the OG site and highlights the role of a serine residue in OG versus G discrimination. The functional significance of Ser308 and its neighboring residues was evaluated by mutational analysis, revealing the critical importance of a β loop in the C-terminal domain for mutation suppression in cells, and biochemical performance <

SUBMITTER: Russelburg LP 

PROVIDER: S-EPMC7069122 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature