6pto
Structure of Ctf4 trimer in complex with three CMG helicases
Structural highlights
FunctionMCM2_YEAST Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity; specifically the MCM2-MCM5 association is proposed to be reversible and to mediate a open ring conformation which may facilitate DNA loading. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity. Necessary for cell growth.[1] [2] Publication Abstract from PubMedThe current view is that eukaryotic replisomes are independent. Here we show that Ctf4 tightly dimerizes CMG helicase, with an extensive interface involving Psf2, Cdc45, and Sld5. Interestingly, Ctf4 binds only one Pol alpha-primase. Thus, Ctf4 may have evolved as a trimer to organize two helicases and one Pol alpha-primase into a replication factory. In the 2CMG-Ctf43-1Pol alpha-primase factory model, the two CMGs nearly face each other, placing the two lagging strands toward the center and two leading strands out the sides. The single Pol alpha-primase is centrally located and may prime both sister replisomes. The Ctf4-coupled-sister replisome model is consistent with cellular microscopy studies revealing two sister forks of an origin remain attached and are pushed forward from a protein platform. The replication factory model may facilitate parental nucleosome transfer during replication. Ctf4 organizes sister replisomes and Pol alpha into a replication factory.,Yuan Z, Georgescu R, Santos RLA, Zhang D, Bai L, Yao NY, Zhao G, O'Donnell ME, Li H Elife. 2019 Oct 7;8. pii: 47405. doi: 10.7554/eLife.47405. PMID:31589141[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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