Title

Mutations for worse or better: low-fidelity DNA Synthesis by SOS DNA polymerase v is a tightly regulated double-edged sword

RIS ID

107502

Publication Details

Jaszczur, M., Bertram, J. G., Robinson, A., van Oijen, A. M., Woodgate, R., Cox, M. M. & Goodman, M. F. (2016). Mutations for worse or better: low-fidelity DNA Synthesis by SOS DNA polymerase v is a tightly regulated double-edged sword. Biochemistry, 55 (16), 2309-2318.

Abstract

1953, the year of Watson and Crick, bore witness to a less acclaimed yet highly influential discovery. Jean Weigle demonstrated that upon infection of Escherichia coli, λ phage deactivated by UV radiation, and thus unable to form progeny, could be reactivated by irradiation of the bacterial host. Evelyn Witkin and Miroslav Radman later revealed the presence of the SOS regulon. The more than 40 regulon genes are repressed by LexA protein and induced by the coproteolytic cleavage of LexA, catalyzed by RecA protein bound to single-stranded DNA, the RecA* nucleoprotein filament. Several SOS-induced proteins are engaged in repairing both cellular and extracellular damaged DNA. There's no "free lunch", however, because error-free repair is accompanied by error-prone translesion DNA synthesis (TLS), involving E. coli DNA polymerase V (UmuD′2C) and RecA*. This review describes the biochemical mechanisms of pol V-mediated TLS. pol V is active only as a mutasomal complex, pol V Mut = UmuD′2C-RecA-ATP. RecA* donates a single RecA subunit to pol V. We highlight three recent insights. (1) pol V Mut has an intrinsic DNA-dependent ATPase activity that governs polymerase binding and dissociation from DNA. (2) Active and inactive states of pol V Mut are determined at least in part by the distinct interactions between RecA and UmuC. (3) pol V is activated by RecA*, not at a blocked replisome, but at the inner cell membrane.

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Link to publisher version (DOI)

http://dx.doi.org/10.1021/acs.biochem.6b00117