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Structural basis for nick recognition by a minimal pluripotent DNA ligase

Nature Structural & Molecular Biology volume 14, pages 770778 (2007) | Download Citation

Abstract

Chlorella virus DNA ligase, the smallest eukaryotic ligase known, has pluripotent biological activity and an intrinsic nick-sensing function, despite having none of the accessory domains found in cellular ligases. A 2.3-Å crystal structure of the Chlorella virus ligase-AMP intermediate bound to duplex DNA containing a 3′-OH–5′-PO4 nick reveals a new mode of DNA envelopment, in which a short surface loop emanating from the OB domain forms a β-hairpin 'latch' that inserts into the DNA major groove flanking the nick. A network of interactions with the 3′-OH and 5′-PO4 termini in the active site illuminates the DNA adenylylation mechanism and the crucial roles of AMP in nick sensing and catalysis. Addition of a divalent cation triggered nick sealing in crystallo, establishing that the nick complex is a bona fide intermediate in the DNA repair pathway.

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Acknowledgements

This paper is inspired by the 40th anniversary of the discovery of viral ATP-dependent DNA ligases by Charles Richardson and Jerry Hurwitz. This work was supported by US National Institutes of Health grants GM63611 (S.S.) and GM61906 (C.D.L.). S.S. is an American Cancer Society Research Professor.

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  1. Molecular Biology and Structural Biology Programs, Sloan-Kettering Institute, New York, New York 10021, USA.

    • Pravin A Nair
    • , Jayakrishnan Nandakumar
    • , Paul Smith
    • , Mark Odell
    • , Christopher D Lima
    •  & Stewart Shuman

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The authors declare no competing financial interests.

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Correspondence to Stewart Shuman.

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https://doi.org/10.1038/nsmb1266

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