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Replication licensing and cancer--a fatal entanglement?
J Julian Blow1, Peter J Gillespie
1Wellcome Trust Centre for Gene Regulation & Expression, University of Dundee, DD1 5EH, UK. j.j.blow@dundee.ac.uk
Nature Reviews. Cancer
|August 30, 2008
Summary
Misregulation of DNA replication licensing proteins, crucial for cell division, occurs early in cancer. This disruption leads to DNA under- or over-replication, potentially causing genetic instability in tumors.
Area of Science:
- Molecular Biology
- Cancer Biology
- Genetics
Background:
- The replication licensing system precisely duplicates chromosomal DNA each cell cycle.
- Inappropriate expression of licensing proteins is observed early in tumorigenesis across various cancers.
Purpose of the Study:
- To explore the link between misregulated replication licensing and oncogene-induced cell proliferation in cancer.
- To understand how replication licensing errors contribute to genetic instability in cancer cells.
Main Methods:
- Review of existing evidence on replication licensing and cancer.
- Analysis of the consequences of misregulated protein expression.
Main Results:
- Misregulation of replication licensing is a consequence of oncogene-induced cell proliferation.
- This misregulation can result in chromosomal DNA under- or over-replication.
Conclusions:
- Misregulated replication licensing is an early event in cancer development.
- Replication errors caused by licensing defects may explain cancer-associated genetic instability.
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