8xgc
From Proteopedia
Structure of yeast replisome associated with FACT and histone hexamer, Composite map
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 PubMedIn eukaryotes, DNA compacts into chromatin through nucleosomes(1,2). Replication of the eukaryotic genome must be coupled to the transmission of the epigenome encoded in the chromatin(3,4). Here we report cryo-electron microscopy structures of yeast (Saccharomyces cerevisiae) replisomes associated with the FACT (facilitates chromatin transactions) complex (comprising Spt16 and Pob3) and an evicted histone hexamer. In these structures, FACT is positioned at the front end of the replisome by engaging with the parental DNA duplex to capture the histones through the middle domain and the acidic carboxyl-terminal domain of Spt16. The H2A-H2B dimer chaperoned by the carboxyl-terminal domain of Spt16 is stably tethered to the H3-H4 tetramer, while the vacant H2A-H2B site is occupied by the histone-binding domain of Mcm2. The Mcm2 histone-binding domain wraps around the DNA-binding surface of one H3-H4 dimer and extends across the tetramerization interface of the H3-H4 tetramer to the binding site of Spt16 middle domain before becoming disordered. This arrangement leaves the remaining DNA-binding surface of the other H3-H4 dimer exposed to additional interactions for further processing. The Mcm2 histone-binding domain and its downstream linker region are nested on top of Tof1, relocating the parental histones to the replisome front for transfer to the newly synthesized lagging-strand DNA. Our findings offer crucial structural insights into the mechanism of replication-coupled histone recycling for maintaining epigenetic inheritance. Parental histone transfer caught at the replication fork.,Li N, Gao Y, Zhang Y, Yu D, Lin J, Feng J, Li J, Xu Z, Zhang Y, Dang S, Zhou K, Liu Y, Li XD, Tye BK, Li Q, Gao N, Zhai Y Nature. 2024 Mar;627(8005):890-897. doi: 10.1038/s41586-024-07152-2. Epub 2024 , Mar 6. PMID:38448592[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Large Structures | Saccharomyces cerevisiae | Gao N | Gao Y | Li N | Yu D | Zhai Y
