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Title: Structural Basis for Nick Recognition by a Minimal Pluripotent DNA Ligase

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-{angstrom} crystal structure of the Chlorella virus ligase-AMP intermediate bound to duplex DNA containing a 3'-OH-5'-PO{sub 4} nick reveals a new mode of DNA envelopment, in which a short surface loop emanating from the OB domain forms a {beta}-hairpin 'latch' that inserts into the DNA major groove flanking the nick. A network of interactions with the 3'-OH and 5'-PO{sub 4} 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.

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
930529
Report Number(s):
BNL-80554-2008-JA
Journal ID: ISSN 1545-9993; TRN: US200904%%770
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nature Structural and Molecular Biology; Journal Volume: 14; Journal Issue: 8
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; CATALYSIS; CATIONS; CHLORELLA; CRYSTAL STRUCTURE; DNA; DNA REPAIR; LIGASES; national synchrotron light source

Citation Formats

Nair,P., Nandakumar, J., Smith, P., Odell, M., Lima, C., and Shuman, S.. Structural Basis for Nick Recognition by a Minimal Pluripotent DNA Ligase. United States: N. p., 2007. Web. doi:10.1038/nsmb1266.
Nair,P., Nandakumar, J., Smith, P., Odell, M., Lima, C., & Shuman, S.. Structural Basis for Nick Recognition by a Minimal Pluripotent DNA Ligase. United States. doi:10.1038/nsmb1266.
Nair,P., Nandakumar, J., Smith, P., Odell, M., Lima, C., and Shuman, S.. Mon . "Structural Basis for Nick Recognition by a Minimal Pluripotent DNA Ligase". United States. doi:10.1038/nsmb1266.
@article{osti_930529,
title = {Structural Basis for Nick Recognition by a Minimal Pluripotent DNA Ligase},
author = {Nair,P. and Nandakumar, J. and Smith, P. and Odell, M. and Lima, C. and Shuman, S.},
abstractNote = {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-{angstrom} crystal structure of the Chlorella virus ligase-AMP intermediate bound to duplex DNA containing a 3'-OH-5'-PO{sub 4} nick reveals a new mode of DNA envelopment, in which a short surface loop emanating from the OB domain forms a {beta}-hairpin 'latch' that inserts into the DNA major groove flanking the nick. A network of interactions with the 3'-OH and 5'-PO{sub 4} 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.},
doi = {10.1038/nsmb1266},
journal = {Nature Structural and Molecular Biology},
number = 8,
volume = 14,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}