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

AbstractHuman 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 (polη, polι, polκ) and extend the distorted primer-terminus (polς). We use NMR spectroscopy to demonstrate that the Rev1 C-terminal domain utilizes independent interaction interfaces to simultaneously bind a fragment of the ’inserter’ polη and Rev7 subunit of the ’extender’ polς, thereby serving as a cassette that may accommodate several polymerases making them instantaneously available for TLS.Structured summary of protein interactionsREV1, 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 Polη-RIR peptide bind by nuclear magnetic resonance (View interaction)REV1, REV3, REV7 and Polη-RIR peptide physically interact by nuclear magnetic resonance (View interaction)