The C-terminal domain of human Rev1 contains independent binding sites for DNA polymerase η and Rev7 subunit of polymerase ζ

Human Rev1 is a translesion synthesis (TLS) DNA polymerase involved in bypass replication across sites of DNA damage and postreplicational gap-filling. Rev1 plays an essential structural role in TLS by providing a binding platform for other TLS polymerases that insert nucleotides across DNA lesions (pol eta, pol iota, pol kappa) and extend the distorted primer-terminus (pol zeta). We use NMR spectroscopy to demonstrate that the Rev1 C-terminal domain utilizes independent interaction interfaces to simultaneously bind a fragment of the 'inserter' pol eta and Rev7 subunit of the 'extender' pol zeta, thereby serving as a cassette that may accommodate several polymerases making them instantaneously available for TLS. Structured summary of protein interactions: REV1, REV3 and REV7 physically interact by nuclear magnetic resonance (View interaction), molecular sieving (View interaction) and isothermal titration calorimetry (View interaction). REV3 and REV7 bind by molecular sieving (View interaction) REV1 and Pol eta-RIR peptide bind by nuclear magnetic resonance (View interaction) REV1, REV3, REV7 and Pol eta-RIR peptide physically interact by nuclear magnetic resonance (View interaction). (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.