2n1g
From Proteopedia
Structure of C-terminal domain of human polymerase Rev1 in complex with PolD3 RIR-motif
Structural highlights
Function[REV1_HUMAN] Deoxycytidyl transferase involved in DNA repair. Transfers a dCMP residue from dCTP to the 3'-end of a DNA primer in a template-dependent reaction. May assist in the first step in the bypass of abasic lesions by the insertion of a nucleotide opposite the lesion. Required for normal induction of mutations by physical and chemical agents.[1] [2] [3] [4] [5] [DPOD3_HUMAN] Required for optimal DNA polymerase delta activity.[6] [7] [8] Publication Abstract from PubMedTranslesion synthesis (TLS) is a mutagenic branch of cellular DNA damage tolerance that enables bypass replication over DNA lesions carried out by specialized low-fidelity DNA polymerases. The replicative bypass of most types of DNA damage is performed in a two-step process of Rev1/Polzeta-dependent TLS. In the first step, a Y-family TLS enzyme, typically Poleta, Poliota, or Polkappa, inserts a nucleotide across a DNA lesion. In the second step, a four-subunit B-family DNA polymerase Polzeta (Rev3/Rev7/PolD2/PolD3 complex) extends the distorted DNA primer-template. The coordinated action of error-prone TLS enzymes is regulated through their interactions with the two scaffold proteins, the sliding clamp PCNA and the TLS polymerase Rev1. Rev1 interactions with all other TLS enzymes are mediated by its C-terminal domain (Rev1-CT), which can simultaneously bind the Rev7 subunit of Polzeta and Rev1-interacting regions (RIRs) from Poleta, Poliota, or Polkappa. In this work, we identified a previously unknown RIR motif in the C-terminal part of PolD3 subunit of Polzeta whose interaction with the Rev1-CT is among the tightest mediated by RIR motifs. Three-dimensional structure of the Rev1-CT/PolD3-RIR complex determined by NMR spectroscopy revealed a structural basis for the relatively high affinity of this interaction. The unexpected discovery of PolD3-RIR motif suggests a mechanism of "inserter" to "extender" DNA polymerase switch upon Rev1/Polzeta-dependent TLS, in which the PolD3-RIR binding to the Rev1-CT (i) helps displace the "inserter" Poleta, Poliota, or Polkappa from its complex with Rev1, and (ii) facilitates assembly of the four-subunit "extender" Polzeta through simultaneous interaction of Rev1-CT with Rev7 and PolD3 subunits. Interaction between the Rev1 C-Terminal Domain and the PolD3 Subunit of Polzeta Suggests a Mechanism of Polymerase Exchange upon Rev1/Polzeta-Dependent Translesion Synthesis.,Pustovalova Y, Magalhaes MT, D'Souza S, Rizzo AA, Korza G, Walker GC, Korzhnev DM Biochemistry. 2016 Apr 5;55(13):2043-53. doi: 10.1021/acs.biochem.5b01282. Epub, 2016 Mar 24. PMID:26982350[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Large Structures | Korzhnev, D | Pustovalova, Y | Pold3 | Rev1 | Transferase
