5u8s | pdb_00005u8s

Structure of eukaryotic CMG helicase at a replication fork

Loading... Status: waiting for Mol* initialization Structural highlights 5u8s is a 10 chain structure with sequence from Saccharomyces cerevisiae S288C and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 6.1Å Ligands: ATP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PSF1_YEAST Required for DNA replication. Functions as part of the GINS complex which plays an essential role in the initiation of DNA replication by binding to DNA replication origins and facilitating the assembly of the DNA replication machinery. Required for the chromatin binding of CDC45. Publication Abstract from PubMed The eukaryotic CMG (Cdc45, Mcm2-7, GINS) helicase consists of the Mcm2-7 hexameric ring along with five accessory factors. The Mcm2-7 heterohexamer, like other hexameric helicases, is shaped like a ring with two tiers, an N-tier ring composed of the N-terminal domains, and a C-tier of C-terminal domains; the C-tier contains the motor. In principle, either tier could translocate ahead of the other during movement on DNA. We have used cryo-EM single-particle 3D reconstruction to solve the structure of CMG in complex with a DNA fork. The duplex stem penetrates into the central channel of the N-tier and the unwound leading single-strand DNA traverses the channel through the N-tier into the C-tier motor, 5'-3' through CMG. Therefore, the N-tier ring is pushed ahead by the C-tier ring during CMG translocation, opposite the currently accepted polarity. The polarity of the N-tier ahead of the C-tier places the leading Pol epsilon below CMG and Pol alpha-primase at the top of CMG at the replication fork. Surprisingly, the new N-tier to C-tier polarity of translocation reveals an unforeseen quality-control mechanism at the origin. Thus, upon assembly of head-to-head CMGs that encircle double-stranded DNA at the origin, the two CMGs must pass one another to leave the origin and both must remodel onto opposite strands of single-stranded DNA to do so. We propose that head-to-head motors may generate energy that underlies initial melting at the origin. Structure of eukaryotic CMG helicase at a replication fork and implications to replisome architecture and origin initiation.,Georgescu R, Yuan Z, Bai L, de Luna Almeida Santos R, Sun J, Zhang D, Yurieva O, Li H, O'Donnell ME Proc Natl Acad Sci U S A. 2017 Jan 17. pii: 201620500. doi:, 10.1073/pnas.1620500114. PMID:28096349 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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