Nucleic Acids Research Advance Access originally published online on October 27, 2006
Nucleic Acids Research 2006 34(20):6023-6033; doi:10.1093/nar/gkl744
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2006, Vol. 34, No. 20 6023-6033
© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Computational Biology |
Proliferating cell nuclear antigen loaded onto double-stranded DNA: dynamics, minor groove interactions and functional implications
1 Department of Chemistry and Biochemistry, Department of Pharmacology, Howard Hughes Medical Institute and Center for Theoretical Biological Physics, University of California—San Diego, 9500 Gilman Drive La Jolla, CA 92093-0365, USA 2 Department of Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute 10550 North Torrey Pines Road, MB4, La Jolla, CA 92037, USA 3 Life Sciences Division, Department of Molecular Biology Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
*To whom correspondence should be addressed. Tel: +1 858 822 0255; Fax: +1 858 534 4974; Email: iivanov{at}mccammon.ucsd.edu
Received July 20, 2006. Revised September 26, 2006. Accepted September 26, 2006.
Proliferating cell nuclear antigen (PCNA) acts as a biologically essential processivity factor that encircles DNA and provides binding sites for polymerase, flap endonuclease-1 (FEN-1) and ligase during DNA replication and repair. We have computationally characterized the interactions of human and Archaeoglobus fulgidus PCNA trimer with double-stranded DNA (ds DNA) using multi-nanosecond classical molecular dynamics simulations. The results reveal the interactions of DNA passing through the PCNA trimeric ring including the contacts formed, overall orientation and motion with respect to the sliding clamp. Notably, we observe pronounced tilting of the axis of dsDNA with respect to the PCNA ring plane reflecting interactions between the DNA phosphodiester backbone and positively charged arginine and lysine residues lining the PCNA inner surface. Covariance matrix analysis revealed a pattern of correlated motions within and between the three equivalent subunits involving the PCNA C-terminal region and linker strand associated with partner protein binding sites. Additionally, principal component analysis identified low frequency global PCNA subunit motions suitable for translocation along duplex DNA. The PCNA motions and interactions with the DNA minor groove, identified here computationally, provide an unexpected basis for PCNA to act in the coordinated handoff of intermediates from polymerase to FEN-1 to ligase during DNA replication and repair.
*Correspondence may also be addressed to John A. Tainer. Tel: +1 858 784 8119; Fax: +1 858 784 2289; Email: jat{at}scripps.edu
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Lopez Castel, A. E. Tomkinson, and C. E. Pearson CTG/CAG Repeat Instability Is Modulated by the Levels of Human DNA Ligase I and Its Interaction with Proliferating Cell Nuclear Antigen: A DISTINCTION BETWEEN REPLICATION AND SLIPPED-DNA REPAIR J. Biol. Chem., September 25, 2009; 284(39): 26631 - 26645. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Kochaniak, S. Habuchi, J. J. Loparo, D. J. Chang, K. A. Cimprich, J. C. Walter, and A. M. van Oijen Proliferating Cell Nuclear Antigen Uses Two Distinct Modes to Move along DNA J. Biol. Chem., June 26, 2009; 284(26): 17700 - 17710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Scouten Ponticelli, J. M. Duzen, and M. D. Sutton Contributions of the individual hydrophobic clefts of the Escherichia coli {beta} sliding clamp to clamp loading, DNA replication and clamp recycling Nucleic Acids Res., May 1, 2009; 37(9): 2796 - 2809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Mayanagi, S. Kiyonari, M. Saito, T. Shirai, Y. Ishino, and K. Morikawa Mechanism of replication machinery assembly as revealed by the DNA ligase-PCNA-DNA complex architecture PNAS, March 24, 2009; 106(12): 4647 - 4652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Schultz-Norton, V. A. Gabisi, Y. S. Ziegler, I. X. McLeod, J. R. Yates, and A. M. Nardulli Interaction of estrogen receptor {alpha} with proliferating cell nuclear antigen Nucleic Acids Res., August 1, 2007; 35(15): 5028 - 5038. [Abstract] [Full Text] [PDF]
|
|