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RecQ helicases: guardian angels of the DNA replication fork

Abstract

Since the original observations made in James German’s Laboratory that Bloom’s syndrome cells lacking BLM exhibit a decreased rate of both DNA chain elongation and maturation of replication intermediates, a large body of evidence has supported the idea that BLM, and other members of the RecQ helicase family to which BLM belongs, play important roles in DNA replication. More recent evidence indicates roles for RecQ helicases in what can broadly be defined as replication fork ‘repair’ processes when, for example, forks encounter lesions or adducts in the template, or when forks stall due to lack of nucleotide precursors. More specifically, several roles in repair of damaged forks via homologous recombination pathways have been proposed. RecQ helicases are generally only recruited to sites of DNA replication following fork stalling or disruption, and they do so in a checkpoint-dependent manner. There, in addition to repair functions, they aid the stabilisation of stalled replication complexes and seem to contribute to the generation and/or transduction of signals that enforce S-phase checkpoints. RecQ helicases also interact physically and functionally with several key players in DNA replication, including RPA, PCNA, FEN1 and DNA polymerase δ. In this paper, we review the evidence that RecQ helicases contribute to the impressively high level of fidelity with which genome duplication is effected.

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Acknowledgement

The authors wish to thank members of the Genome Integrity Group for useful discussions, Drs. K. Hanada, P. McHugh and L. Wu for critical reading of the manuscript, and Miss E. Weston for preparation of the manuscript. This work was supported by the Cancer Research UK.

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Correspondence to Ian D. Hickson.

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Communicated by E.A. Nigg

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Bachrati, C.Z., Hickson, I.D. RecQ helicases: guardian angels of the DNA replication fork. Chromosoma 117, 219–233 (2008). https://doi.org/10.1007/s00412-007-0142-4

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Keywords

  • Replication Fork
  • Helicase Activity
  • Holliday Junction
  • Stall Replication Fork
  • RecQ Helicases