Endogenous DNA double-strand breaks: Production, fidelity of repair, and induction of cancer
AUTOR(ES)
Vilenchik, Michael M.
FONTE
National Academy of Sciences
RESUMO
This article extends our previous quantitative analysis of the relationship between the dynamics of the primary structure of DNA and mutagenesis associated with single-strand lesions to an analysis of the production and processing of endogenous double-strand breaks (EDSBs) and to their implications for oncogenesis. We estimate that in normal human cells ≈1% of single-strand lesions are converted to ≈50 EDSBs per cell per cell cycle. This number is similar to that for EDSBs produced by 1.5–2.0 Gy of sparsely ionizing radiation. Although EDSBs are usually repaired with high fidelity, errors in their repair contribute significantly to the rate of cancer in humans. The doubling dose for induced DSBs is similar to doubling doses for mutation and for the induction of carcinomas by ionizing radiation. We conclude that rates of production of EDSBs and of ensuing spontaneous mitotic recombination events can account for a substantial fraction of the earliest oncogenic events in human carcinomas.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=240711Documentos Relacionados
- Molecular recombination and the repair of DNA double-strand breaks in CHO cells.
- Multiple Pathways for Repair of DNA Double-Strand Breaks in Mammalian Chromosomes
- The ubiquitin landscape at DNA double-strand breaks
- Tying synaptonemal complex initiation to the formation and programmed repair of DNA double-strand breaks
- Enzymatic induction of DNA double-strand breaks in gamma-irradiated Escherichia coli K-12.