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Milestone 22

Indirect but just as effective

Mechanisms of genetic instability in cancer

Nature Reviews Cancer volume 6, pages S21–S22 (2006)Cite this article

Although many cancers result from mutations in prototype oncogenes and tumour-suppressor genes that regulate cell proliferation and apoptosis (see Milestones 10, 11, 12, 20 and 21), cancer can also arise indirectly from defects in the protective cellular mechanisms that repair DNA damage. This idea originated in the study by Theodor Boveri of chromosomal imbalances in somatic cells (see Milestone 2). The type of DNA damage can range from the subtle, such as a single unrepaired base lesion, through small deletions or insertions, to macroscopic changes that manifest as non-reciprocal chromosome translocations (see Milestone 10). Genetic instability at any of these levels can predispose to cancer by increasing the rate at which potentially oncogenic mutations and chromosomal alterations occur.

When cells are exposed to ultraviolet (UV) light, base adducts are formed that must be excised for replication to occur. This process, nucleotide-excision repair (NER), involves recognition of distortion of the DNA helix, assembly of a complex on and around the lesion, and excision of a single-strand fragment containing the modified base. Several human syndromes show UV hypersensitivity, and one, xeroderma pigmentosum (XP), displays a strong predisposition to skin cancer.

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    Angela K. Eggleston

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  1. Angela K. Eggleston
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Eggleston, A. Indirect but just as effective. Nat Rev Cancer 6 (Suppl 1), S21–S22 (2006). https://doi.org/10.1038/nrc1864

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