Human DNA polymerase β, but not λ, can bypass a 2-deoxyribonolactone lesion together with proliferating cell nuclear antigen.

Abstract:

The C1'-oxidized lesion 2-deoxyribonolactone (L) is induced by free radical attack of DNA. This lesion is mutagenic, inhibits base excision repair, and can lead to strand scission. In double stranded DNA L is repaired by long-patch base excision repair, but it induces replication fork arrest in a single-strand template. Translesion synthesis requires a specialized DNA polymerase (Pol). In E. coli, Pol V is responsible for bypassing L, while in yeast Pol ζ has been shown to be required for efficient bypass. Very little is known about the identity of human Pols capable of bypassing L. For instance, the activity of family X enzymes has never been investigated. We examined the ability of different family X Pols: Pols β, λ and TdT from human cells and Pol IV from S. cerevisiae to act on DNA containing an isolated 2-deoxyribonolactone, as well as when the lesion comprises the 5'-component of a tandem lesion. We show that Pol β, but not Pol λ, can bypass a single L lesion in the template, and its activity is increased by the auxiliary protein proliferating cell nuclear antigen (PCNA), while both enzymes were completely blocked by a tandem lesion. Yeast Pol IV was able to bypass the single L and the tandem lesion but with little nucleotide insertion specificity. Finally, L did not affect the polymerization activity of the template-independent enzyme TdT.

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