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Control of DNA replication and its potential clinical exploitation

Nature Reviews Cancer volume 5, pages 135–141 (2005)Cite this article

Abstract

Multiple conserved mechanisms limit DNA replication to once per cell cycle. One vital level of control focuses on the loading of the heterohexameric ring of minichromosome maintenance proteins (MCMs) onto chromatin in the hierarchical assembly of the pre-replication complex at origins of replication. An essential role in proliferation for MCMs and their regulators makes them potentially important biomarkers for routine clinical use in cancer detection and prognosis.

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Figure 1: Factors regulating the binding of minichromosome maintenance proteins (MCMs) to chromatin.
Figure 2: Minichromosome maintenance proteins (MCMs) detect cells in cycle in normal and pre-malignant cervical tissue.
Figure 3: Novel methods for histological assessment of cell-cycle state and rate of cycling.

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Acknowledgements

We would like to thank L. Morris for helpful discussions and contributing the micrographs in Fig. 2 and L.K. Ferrigno for critical review of the manuscript. M.A.G. is supported by a Medical Research Council Clinical Research Training Fellowship and K.K.T. is supported by a Medical Research Council Pre-Doctoral Fellowship.

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Authors and Affiliations

  1. the Medical Research Council Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge, CB2 2XZ, UK

    Michael A. Gonzalez, Kiku-e K. Tachibana, Ronald A. Laskey & Nicholas Coleman

Authors
  1. Michael A. Gonzalez
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  2. Kiku-e K. Tachibana
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  3. Ronald A. Laskey
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Corresponding authors

Correspondence to Michael A. Gonzalez or Nicholas Coleman.

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Competing interests

N.C. and R.A.L. are entitled to a share of royalties received by Cancer Research Technology Ltd on sales of products related to the use of MCM detection in cancer diagnosis.

Related links

Related links

DATABASES

Entrez Gene

CCND1

CDC6

CDK1

CDK2

CDK4

CDK6

CDT1

geminin

INK4A

INK4B

INK4C

INK4D

KIP1

KIP2

MCM2

MCM4

MCM5

MCM6

WAF1

National Cancer Institute

bladder cancer

brain tumour

breast cancer

cervical cancer

non-small cell lung cancer

oesophageal cancer

oral squamous cell carcinoma

prostate cancer

renal cell cancer

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Gonzalez, M., Tachibana, Ke., Laskey, R. et al. Control of DNA replication and its potential clinical exploitation. Nat Rev Cancer 5, 135–141 (2005). https://doi.org/10.1038/nrc1548

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