Title

Polymerase exchange on single DNA molecules reveals processivity clamp control of translesion synthesis

RIS ID

91008

Publication Details

Kath, J. E., Jergic, S., Heltzel, J. M. H., Jacob, D. T., Dixon, N. E., Sutton, M. D., Walker, G. C. & Loparo, J. J. (2014). Polymerase exchange on single DNA molecules reveals processivity clamp control of translesion synthesis. Proceedings of the National Academy of Sciences of USA, 111 (21), 7647-7652.

Abstract

Translesion synthesis (TLS) by Y-family DNA polymerases alleviates replication stalling at DNA damage. Ring-shaped processivity clamps play a critical but ill-defined role in mediating exchange between Y-family and replicative polymerases during TLS. By reconstituting TLS at the single-molecule level, we show that the Escherichia coli β clamp can simultaneously bind the replicative polymerase (Pol) III and the conserved Y-family Pol IV, enabling exchange of the two polymerases and rapid bypass of a Pol IV cognate lesion. Furthermore, we find that a secondary contact between Pol IV and β limits Pol IV synthesis under normal conditions but facilitates Pol III displacement from the primer terminus following Pol IV induction during the SOS DNA damage response. These results support a role for secondary polymerase clamp interactions in regulating exchange and establishing a polymerase hierarchy.

Grant Number

ARC/DP0877658

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