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Structural basis for nick recognition by a minimal pluripotent DNA ligase

Nair, Pravin A. and Nandakumar, Jayakrishnan and Smith, Paul and Odell, Mark and Lima, Christopher D. and Shuman, Stewart (2007) Structural basis for nick recognition by a minimal pluripotent DNA ligase. Nature Structural and Molecular Biology, 14 (8). pp. 770-778. ISSN 1545-9993

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Official URL: http://dx.doi.org/10.1038/nsmb1266

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 -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.

Item Type:Article
Research Community:University of Westminster > Life Sciences, School of
ID Code:4419
Deposited On:17 Jul 2007
Last Modified:07 Apr 2008 14:33

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