Death comes in small packages

Killer sunburns are detected by the smallest of genes, according to Bruce McKay and colleagues (Ottawa Regional Cancer Centre, Ottawa, ON). A bias toward damage of larger genes leaves intact only the tiny genes, which make sure that overdamaged cells die.Figure The transcription of survival genes (white boxes) doesn't survive high UV (right).UV rays create DNA lesions that block RNA polymerases. A little damage can be cleaned up by UV-induced repair pathways that remove the lesions. But too much UV—which may make more lesions than can be repaired—triggers apoptosis instead. McKay now shows that the small size of apoptotic genes means that they rule when UV levels are high. The authors find that fewer genes are transcribed as UV levels increase, and those that are transcribed are smaller, with fewer and shorter introns. These small genes include many known mitochondrial apoptotic genes, which were activated at the highest UV dose tested. Genes encoding repair proteins or survival proteins, such as Bcl-XL, were induced only at low UV levels, probably because they are larger and more likely to suffer from transcription-blocking lesions. “The shift in the pattern of gene expression is the result of a passive mechanism,” says McKay. So no extra energy is needed to convince highly injured cells to die. ▪ Reference: McKay, B., et al. 2004. Proc. Natl. Acad. Sci. USA. 10.1073/pnas.0308181101. [PMC free article] [PubMed]