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Philosophical Transactions of the Royal Society B: Biological Sciences logoLink to Philosophical Transactions of the Royal Society B: Biological Sciences
. 2004 Jan 29;359(1441):25–30. doi: 10.1098/rstb.2003.1361

Protein trafficking on sliding clamps.

Francisco López de Saro 1, Roxana E Georgescu 1, Frank Leu 1, Mike O'Donnell 1
PMCID: PMC1693307  PMID: 15065653

Abstract

The sliding clamps of chromosomal replicases are acted upon by both the clamp loader and DNA polymerase. Several other proteins and polymerases also interact with the clamp. These proteins bind the clamp at the same spot and use it in sequential fashion. First the clamp loader must bind the clamp in order to load it onto DNA, but directly thereafter the clamp loader must clear away from the clamp so it can be used by the replicative DNA polymerase. At the end of replication, the replicase is ejected from the clamp, which presumably allows the clamp to interact with yet other proteins after its use by the replicase. This paper describes how different proteins in the Escherichia coli replicase, DNA polymerase III holoenzyme, coordinate their traffic flow on the clamp. The mechanism by which traffic flow on the beta clamp is directed is based on competition of the proteins for the clamp, where DNA structure modulates the competition. It seems likely that the principles will generalize to a traffic flow of other factors on these circular clamp proteins.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baker T. A., Bell S. P. Polymerases and the replisome: machines within machines. Cell. 1998 Feb 6;92(3):295–305. doi: 10.1016/s0092-8674(00)80923-x. [DOI] [PubMed] [Google Scholar]
  2. Flower A. M., McHenry C. S. The gamma subunit of DNA polymerase III holoenzyme of Escherichia coli is produced by ribosomal frameshifting. Proc Natl Acad Sci U S A. 1990 May;87(10):3713–3717. doi: 10.1073/pnas.87.10.3713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gulbis J. M., Kelman Z., Hurwitz J., O'Donnell M., Kuriyan J. Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human PCNA. Cell. 1996 Oct 18;87(2):297–306. doi: 10.1016/s0092-8674(00)81347-1. [DOI] [PubMed] [Google Scholar]
  4. Jeruzalmi D., Yurieva O., Zhao Y., Young M., Stewart J., Hingorani M., O'Donnell M., Kuriyan J. Mechanism of processivity clamp opening by the delta subunit wrench of the clamp loader complex of E. coli DNA polymerase III. Cell. 2001 Aug 24;106(4):417–428. [PubMed] [Google Scholar]
  5. Jeruzalmi David, O'Donnell Mike, Kuriyan John. Clamp loaders and sliding clamps. Curr Opin Struct Biol. 2002 Apr;12(2):217–224. doi: 10.1016/s0959-440x(02)00313-5. [DOI] [PubMed] [Google Scholar]
  6. Kim S., Dallmann H. G., McHenry C. S., Marians K. J. Coupling of a replicative polymerase and helicase: a tau-DnaB interaction mediates rapid replication fork movement. Cell. 1996 Feb 23;84(4):643–650. doi: 10.1016/s0092-8674(00)81039-9. [DOI] [PubMed] [Google Scholar]
  7. Kong X. P., Onrust R., O'Donnell M., Kuriyan J. Three-dimensional structure of the beta subunit of E. coli DNA polymerase III holoenzyme: a sliding DNA clamp. Cell. 1992 May 1;69(3):425–437. doi: 10.1016/0092-8674(92)90445-i. [DOI] [PubMed] [Google Scholar]
  8. Krishna T. S., Kong X. P., Gary S., Burgers P. M., Kuriyan J. Crystal structure of the eukaryotic DNA polymerase processivity factor PCNA. Cell. 1994 Dec 30;79(7):1233–1243. doi: 10.1016/0092-8674(94)90014-0. [DOI] [PubMed] [Google Scholar]
  9. Lenne-Samuel Nathalie, Wagner Jérôme, Etienne Hélène, Fuchs Robert P. P. The processivity factor beta controls DNA polymerase IV traffic during spontaneous mutagenesis and translesion synthesis in vivo. EMBO Rep. 2001 Dec 19;3(1):45–49. doi: 10.1093/embo-reports/kvf007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Leu Frank P., Georgescu Roxana, O'Donnell Mike. Mechanism of the E. coli tau processivity switch during lagging-strand synthesis. Mol Cell. 2003 Feb;11(2):315–327. doi: 10.1016/s1097-2765(03)00042-x. [DOI] [PubMed] [Google Scholar]
  11. López de Saro F. J., O'Donnell M. Interaction of the beta sliding clamp with MutS, ligase, and DNA polymerase I. Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8376–8380. doi: 10.1073/pnas.121009498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. McHenry C. S. Purification and characterization of DNA polymerase III'. Identification of tau as a subunit of the DNA polymerase III holoenzyme. J Biol Chem. 1982 Mar 10;257(5):2657–2663. [PubMed] [Google Scholar]
  13. Moarefi I., Jeruzalmi D., Turner J., O'Donnell M., Kuriyan J. Crystal structure of the DNA polymerase processivity factor of T4 bacteriophage. J Mol Biol. 2000 Mar 10;296(5):1215–1223. doi: 10.1006/jmbi.1999.3511. [DOI] [PubMed] [Google Scholar]
  14. Naktinis V., Turner J., O'Donnell M. A molecular switch in a replication machine defined by an internal competition for protein rings. Cell. 1996 Jan 12;84(1):137–145. doi: 10.1016/s0092-8674(00)81000-4. [DOI] [PubMed] [Google Scholar]
  15. O'Donnell M., Jeruzalmi D., Kuriyan J. Clamp loader structure predicts the architecture of DNA polymerase III holoenzyme and RFC. Curr Biol. 2001 Nov 13;11(22):R935–R946. doi: 10.1016/s0960-9822(01)00559-0. [DOI] [PubMed] [Google Scholar]
  16. Shamoo Y., Steitz T. A. Building a replisome from interacting pieces: sliding clamp complexed to a peptide from DNA polymerase and a polymerase editing complex. Cell. 1999 Oct 15;99(2):155–166. doi: 10.1016/s0092-8674(00)81647-5. [DOI] [PubMed] [Google Scholar]
  17. Stukenberg P. T., Turner J., O'Donnell M. An explanation for lagging strand replication: polymerase hopping among DNA sliding clamps. Cell. 1994 Sep 9;78(5):877–887. doi: 10.1016/s0092-8674(94)90662-9. [DOI] [PubMed] [Google Scholar]
  18. Tang M., Pham P., Shen X., Taylor J. S., O'Donnell M., Woodgate R., Goodman M. F. Roles of E. coli DNA polymerases IV and V in lesion-targeted and untargeted SOS mutagenesis. Nature. 2000 Apr 27;404(6781):1014–1018. doi: 10.1038/35010020. [DOI] [PubMed] [Google Scholar]
  19. Tang M., Shen X., Frank E. G., O'Donnell M., Woodgate R., Goodman M. F. UmuD'(2)C is an error-prone DNA polymerase, Escherichia coli pol V. Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8919–8924. doi: 10.1073/pnas.96.16.8919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Tsuchihashi Z., Kornberg A. Translational frameshifting generates the gamma subunit of DNA polymerase III holoenzyme. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2516–2520. doi: 10.1073/pnas.87.7.2516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Warbrick E. The puzzle of PCNA's many partners. Bioessays. 2000 Nov;22(11):997–1006. doi: 10.1002/1521-1878(200011)22:11<997::AID-BIES6>3.0.CO;2-#. [DOI] [PubMed] [Google Scholar]
  22. Yuzhakov A., Kelman Z., O'Donnell M. Trading places on DNA--a three-point switch underlies primer handoff from primase to the replicative DNA polymerase. Cell. 1999 Jan 8;96(1):153–163. doi: 10.1016/s0092-8674(00)80968-x. [DOI] [PubMed] [Google Scholar]
  23. Yuzhakov A., Turner J., O'Donnell M. Replisome assembly reveals the basis for asymmetric function in leading and lagging strand replication. Cell. 1996 Sep 20;86(6):877–886. doi: 10.1016/s0092-8674(00)80163-4. [DOI] [PubMed] [Google Scholar]

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