4gk5 | pdb_00004gk5

Crystal structure of human Rev3-Rev7-Rev1-Polkappa complex

spinqualitylabelsall models 4gk5, resolution 3.21Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4gk5 is a 7 chain structure with sequence from Clostridium acetobutylicum and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 4gk0 Gene: MAD2L2, MAD2B, REV7 (Homo sapiens), REV3L, POLZ, REV3 (Clostridium acetobutylicum), REV1, REV1L (Homo sapiens) Activity: DNA-directed DNA polymerase, with EC number 2.7.7.7 Resources: FirstGlance, OCA, RCSB, PDBsum Function [POLK_HUMAN] DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Depending on the context, it inserts the correct base, but causes frequent base transitions, transversions and frameshifts. Lacks 3'-5' proofreading exonuclease activity. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity. [MD2L2_HUMAN] Adapter protein able to interact with different proteins and involved in different biological processes. Mediates the interaction between the error-prone DNA polymerase zeta catalytic subunit REV3L and the inserter polymerase REV1, thereby mediating the second polymerase switching in translesion DNA synthesis. Translesion DNA synthesis releases the replication blockade of replicative polymerases, stalled in presence of DNA lesions. May also regulate another aspect of cellular response to DNA damage through regulation of the JNK-mediated phosphorylation and activation of the transcriptional activator ELK1. Inhibits the FZR1- and probably CDC20-mediated activation of the anaphase promoting complex APC thereby regulating progression through the cell cycle. Regulates TCF7L2-mediated gene transcription and may play a role in epithelial-mesenchymal transdifferentiation. [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. [DPOLZ_HUMAN] Interacts with MAD2L2 to form the error prone DNA polymerase zeta involved in translesion DNA synthesis. Publication Abstract from PubMed In addition to DNA repair pathways, cells utilize translesion DNA synthesis (TLS) to bypass DNA lesions during replication. During TLS, Y-family DNA polymerase (Poleta, Polkappa, Poli and Rev1) inserts specific nucleotide opposite preferred DNA lesions, and then Polzeta consisting of two subunits, Rev3 and Rev7, carries out primer extension. Here, we report the complex structures of Rev3-Rev7-Rev1(CTD) and Rev3-Rev7-Rev1(CTD)-Polkappa(RIR). These two structures demonstrate that Rev1(CTD) contains separate binding sites for Polkappa and Rev7. Our BIAcore experiments provide additional support for the notion that the interaction between Rev3 and Rev7 increases the affinity of Rev7 and Rev1. We also verified through FRET experiment that Rev1, Rev3, Rev7 and Polkappa form a stable quaternary complex in vivo, thereby suggesting an efficient switching mechanism where the "inserter" polymerase can be immediately replaced by an "extender" polymerase within the same quaternary complex. Structural insights into the assembly of human translesion polymerase complexes.,Xie W, Yang X, Xu M, Jiang T Protein Cell. 2012 Nov;3(11):864-74. doi: 10.1007/s13238-012-2102-x. Epub 2012, Nov 10. PMID:23143872 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA polymerase

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