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    CUL2(LRR1) , TRAIP and p97 control CMG helicase disassembly in the mammalian cell cycle

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    Authors
    Villa, F.
    Fujisawa, R.
    Ainsworth, J.
    Nishimura, K.
    Lie-A-Ling, Michael
    Lacaud, Georges
    Labib, K. P.
    Affiliation
    The MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee
    Issue Date
    2021
    
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    Abstract
    The eukaryotic replisome is disassembled in each cell cycle, dependent upon ubiquitylation of the CMG helicase. Studies of Saccharomyces cerevisiae, Caenorhabditis elegans and Xenopus laevis have revealed surprising evolutionary diversity in the ubiquitin ligases that control CMG ubiquitylation, but regulated disassembly of the mammalian replisome has yet to be explored. Here, we describe a model system for studying the ubiquitylation and chromatin extraction of the mammalian CMG replisome, based on mouse embryonic stem cells. We show that the ubiquitin ligase CUL2LRR1 is required for ubiquitylation of the CMG-MCM7 subunit during S-phase, leading to disassembly by the p97 ATPase. Moreover, a second pathway of CMG disassembly is activated during mitosis, dependent upon the TRAIP ubiquitin ligase that is mutated in primordial dwarfism and mis-regulated in various cancers. These findings indicate that replisome disassembly in diverse metazoa is regulated by a conserved pair of ubiquitin ligases, distinct from those present in other eukaryotes.
    Citation
    Villa F, Fujisawa R, Ainsworth J, Nishimura K, Lie ALM, Lacaud G, et al. CUL2(LRR1) , TRAIP and p97 control CMG helicase disassembly in the mammalian cell cycle. EMBO Rep. 2021;22(3):e52164.
    Journal
    EMBO Reports
    URI
    http://hdl.handle.net/10541/623884
    DOI
    10.15252/embr.202052164
    PubMed ID
    33590678
    Additional Links
    https://dx.doi.org/10.15252/embr.202052164
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.15252/embr.202052164
    Scopus Count
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    All Paterson Institute for Cancer Research

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