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The ring-shaped hexameric helicases that function at DNA replication forks


DNA replication requires separation of genomic duplex DNA strands, an operation that is performed by a hexameric ring-shaped helicase in all domains of life. The structures and chemomechanical actions of these fascinating machines are coming into sharper focus. Although there is no evolutionary relationship between the hexameric helicases of bacteria and those of archaea and eukaryotes, they share many fundamental features. Here we review recent studies of these two groups of hexameric helicases and the unexpected distinctions they have also unveiled.

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Fig. 1: Overview of replicative hexameric helicases.
Fig. 2: Rotary-staircase model of translocation by hexameric helicases.
Fig. 3: Structures of hexameric helicases bound to single-stranded nucleic acid.
Fig. 4: CMG-forked DNA structures with the N tier leading the C tier during translocation.


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We are grateful to N. Yao (Rockefeller University) and L. Bai (Van Andel Research Institute) for making some of the illustrations in this review. This work was supported by grants from the NIH (GM111472 and GM124170 (to H.L.) and GM115809 (to M.O’D.)), the Van Andel Research Institute (H.L.) and the Howard Hughes Medical Institute (M.O’D.). We thank members of the O’Donnell lab and the Li lab for their contribution to some of the studies described here.

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O’Donnell, M., Li, H. The ring-shaped hexameric helicases that function at DNA replication forks. Nat Struct Mol Biol 25, 122–130 (2018).

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