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A tale of toroids in DNA metabolism

Nature Reviews Molecular Cell Biology volume 1, pages 22–30 (2000)Cite this article

Abstract

A strikingly large number of the proteins involved in DNA metabolism adopt a toroidal ? or ring-shaped ? quaternary structure, even though they have completely unrelated functions. Given that these proteins all use DNA as a substrate, their convergence to one shape is probably not a coincidence. Ring-forming proteins may have been selected during evolution for advantages conferred by the toroidal shape on their interactions with DNA.

Key Points

  • A strikingly large number of proteins that interact with DNA assume a toroidal, or ring-shaped structure. These include sliding clamp proteins, which increase the lifetime of other proteins on DNA, helicases that unwind DNA, topisomerases that alter DNA structure, and many other proteins that mediate the processes of DNA replication, repair and recombination.

  • A common feature of these proteins is that their subunits are arranged in a closed ring, the centre of which is able to accommodate single stranded and/or duplex DNA. For many proteins, this property is proposed to allow high processivity on DNA through topological linkage.

  • Although some proteins such as human topoisomerase I bind DNA in the central cavity simply by opening up and closing around DNA, others require the help of ?molecular matchmakers? that link toroidal proteins and DNA by ATP-dependent reactions.

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Figure 1: Circular sliding clamps.
Figure 2: Circular helicases.
Figure 3: Circular recombination proteins.
Figure 4: Circular topoisomerases.
Figure 5: More circular proteins.

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Acknowledgements

We thank all researchers who provided images, including J. Kuriyan and D. Jeruzalmi (E. coli β clamp, yPCNA, T4 gp45); Y. Shamoo and T. Steitz (RB69 clamp and polymerase); T. Ellenberger (T7 gp4); E. Gogol (T4 gp41); E. Egelman (E. coli DnaB, RuvB, rho, BPV E1, phage λ β protein, hDmc1, hRad52); C. San Martin (SV40 T antigen); I. Hickson (BLM helicase); J. Chong and B. Stillman (M. th MCM); Y. Ishimi (human MCM); P. Ahnert (T7 gp4 on DNA); R. Kovall and B. Matthews (phage λ exonuclease); M. Redinbo and W. Hol (human topoI); A. Mondragón (E. coli topoI and topoIII); J. Wang (yeast topoII); J. Y. Lee and S. W. Suh (DNA ligase); A. Anston (TRAP); J. Carrascosa (φ29 connector) and M. Kasai (human translin). We also thank M. Davey and K. Picha for discussions. Work supported by a grant from the NIH to M.O.

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Authors and Affiliations

  1. The Rockefeller University, 1230 York Avenue, New York, 10021, New York, USA

    Manju M. Hingorani & Mike O'Donnell

  2. The Howard Hughes Medical Institute, 1230 York Avenue, New York, 10021 , New York, USA

    Mike O'Donnell

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  1. Manju M. Hingorani
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Related links

Related links

DATABASE LINKS

Bloom's syndrome

BLM helicase

DMC1

RAD52

translin

Cdc6

hPCNA

Fen1

DNA ligase 1

DNA methyltransferase

XPG

RAD51

RFC complex

human topisomerases

F1-ATPase

DnaB helicase

DnaC

Rho

RecA

E. coli topisomerase

S. cerevisiae topisomerase II

ENCYCLOPEDIA OF LIFE SCIENCES

DNA helicases

Polymerase processivity

Glossary

PROCESSIVITY

The ability of an enzyme to catalyse more than one turnover before releasing the substrate or product of the reaction.

REPLISOME

The multi-protein assembly at the junction of the DNA replication fork.

STRAND EXCHANGE

The process by which a single DNA strand switches from one duplex DNA molecule to base pair with a complementary strand from a second, homologous duplex DNA molecule.

HOMOLOGOUS RECOMBINATION

The process by which segments of DNA are exchanged between two DNA duplexes that share high sequence similarity.

CATENATION/DECATENATION

Topoisomerases catenate (join) or decatenate (separate) two circular DNA molecules by cutting one DNA strand, passing a second strand through the break, and resealing the break in DNA.

MOLECULAR MATCHMAKER

A macromolecule that increases the affinity of two or more other molecules for each other, usually through a reaction using energy from ATP binding and hydrolysis.

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Hingorani, M., O'Donnell, M. A tale of toroids in DNA metabolism. Nat Rev Mol Cell Biol 1, 22–30 (2000). https://doi.org/10.1038/35036044

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