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Replication licensing and cancer — a fatal entanglement?

Abstract

Correct regulation of the replication licensing system ensures that chromosomal DNA is precisely duplicated in each cell division cycle. Licensing proteins are inappropriately expressed at an early stage of tumorigenesis in a wide variety of cancers. Here we discuss evidence that misregulation of replication licensing is a consequence of oncogene-induced cell proliferation. This misregulation can cause either under- or over-replication of chromosomal DNA, and could explain the genetic instability commonly seen in cancer cells.

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Figure 1: Overview of origin licensing during the cell division cycle.
Figure 2: Minichromosome maintenance 5 (MCM5) in normal and dysplastic cervical epithelium.
Figure 3: The DNA damage response.
Figure 4: Consequences of re-replication.
Figure 5: Dormant origins and replication fork stalling.

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Acknowledgements

The authors are funded by Cancer Research UK grants C303/A7399 (J.J.B.) and C303/A5434 (P.J.G.).

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Correspondence to J. Julian Blow.

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J.J.B. is a named inventor on UK Patent GB2404441: “Assay methods relating to the action of geminin in the licensing of DNA replication complexes in transformed cells.”

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Blow, J., Gillespie, P. Replication licensing and cancer — a fatal entanglement?. Nat Rev Cancer 8, 799–806 (2008). https://doi.org/10.1038/nrc2500

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