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Terminating the replication helicase

Nature Cell Biology volume 19, pages 410–412 (2017)Cite this article

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A feature of the cell cycle is that the events of one cycle must be reset before the next one begins. A study now shows that the replication machinery is removed from fully replicated DNA by a conserved ubiquitin- and CDC48 (also known as p97)-dependent pathway. This explains how eukaryotic chromosomes are returned to the unreplicated state.

All organisms must make a perfect copy of the genome during every cell division. For eukaryotes this involves separating the steps of DNA replication into distinct cell cycle phases. Although great strides have been made in understanding how DNA replication is initiated, we understand very little about what happens when two replication forks converge to terminate this process. Clarifying the final steps of replication is important to appreciate how DNA is fully replicated and segregated in a timely manner. Recent work now identifies an evolutionarily conserved pathway involving the E3 ubiquitin ligase complex CRL2Lrr1 (CRL2LRR-1 in Caenorhabditis elegans, and CRL2LRR1 in Xenopus laevis) that is required for the removal of the replication apparatus when DNA synthesis is complete1,2. These studies begin to explain how DNA replication is irreversibly reset before the next division.

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Figure 1: The MCM helicase cycle within the cell cycle.
Figure 2: At least two pathways target terminated CMG complexes in C. elegans.

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Authors and Affiliations

  1. Vincent Gaggioli and Philip Zegerman are at the Wellcome Trust/Cancer Research UK Gurdon Institute and the Department of Biochemistry, The Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Cambridge CB2 1QN, UK,

    Vincent Gaggioli & Philip Zegerman

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  1. Vincent Gaggioli
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  2. Philip Zegerman
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Correspondence to Philip Zegerman.

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Gaggioli, V., Zegerman, P. Terminating the replication helicase. Nat Cell Biol 19, 410–412 (2017). https://doi.org/10.1038/ncb3519

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