Journal Article

<i>CDC6</i>: from DNA replication to cell cycle checkpoints and oncogenesis

Luis R. Borlado and Juan Méndez

in Carcinogenesis

Volume 29, issue 2, pages 237-243
Published in print February 2008 | ISSN: 0143-3334
Published online November 2007 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgm268
CDC6: from DNA replication to cell cycle checkpoints and oncogenesis

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Cell division cycle 6 (CDC6) is an essential regulator of DNA replication in eukaryotic cells. Its best-characterized function is the assembly of prereplicative complexes at origins of replication during the G1 phase of the cell division cycle. However, CDC6 also plays important roles in the activation and maintenance of the checkpoint mechanisms that coordinate S phase and mitosis, and recent studies have unveiled its proto-oncogenic activity. CDC6 overexpression interferes with the expression of INK4/ARF tumor suppressor genes through a mechanism involving the epigenetic modification of chromatin at the INK4/ARF locus. In addition, CDC6 overexpression in primary cells may promote DNA hyperreplication and induce a senescence response similar to that caused by oncogene activation. These findings indicate that deregulation of CDC6 expression in human cells poses a serious risk of carcinogenesis.

Journal Article.  6465 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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