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The RFC Clamp Loader: Structure and Function

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The Eukaryotic Replisome: a Guide to Protein Structure and Function

Part of the book series: Subcellular Biochemistry ((SCBI,volume 62))

Abstract

The eukaryotic RFC clamp loader couples the energy of ATP hydrolysis to open and close the circular PCNA sliding clamp onto primed sites for use by DNA polymerases and repair factors. Structural studies reveal clamp loaders to be heteropentamers. Each subunit contains a region of homology to AAA+ proteins that defines two domains. The AAA+ domains form a right-handed spiral upon binding ATP. This spiral arrangement generates a DNA binding site within the center of RFC. DNA enters the central chamber through a gap between the AAA+ domains of two subunits. Specificity for a primed template junction is achieved by a third domain that blocks DNA, forcing it to bend sharply. Thus only DNA with a flexible joint can bind the central chamber. DNA entry also requires a slot in the PCNA clamp, which is opened upon binding the AAA+ domains of the clamp loader. ATP hydrolysis enables clamp closing and ejection of RFC, completing the clamp loading reaction.

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  1. Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA

    Nina Y. Yao & Mike O’Donnell

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  1. Nina Y. Yao
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  2. Mike O’Donnell
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Correspondence to Nina Y. Yao .

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  1. , School of Biology, University of St Andrews, Biomedical Sciences Research Complex, North Haugh, St Andrews, KY16 9ST, Fife, United Kingdom

    Stuart MacNeill

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Yao, N.Y., O’Donnell, M. (2012). The RFC Clamp Loader: Structure and Function. In: MacNeill, S. (eds) The Eukaryotic Replisome: a Guide to Protein Structure and Function. Subcellular Biochemistry, vol 62. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4572-8_14

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