Early insights into DNA repair came from the study of children with xeroderma pigmentosum (XP), a rare, genetically inherited disease. For youngsters with this condition, brief exposure to even normal daylight rapidly leads to skin cancer and other malignancies. Some call this ultraphotosensitive group "moon children" because on the occasions when they venture outside they must wear head-to-toe UV-proof suits. No cure for XP exists, and few patients survive to adulthood.
In 1968, James E. Cleaver, a professor of dermatology at the University of California, San Francisco, discovered that XP patients lack an essential mechanism, known as excision repair, that in normal individuals acts to correct solar damage to the skin's DNA. He showed that, absent this damage-repair mechanism, the skin cells of moon children continue to replicate their UV-damaged DNA. Those cells can then mutate into cancerous forms, leading to tumors or neurodegenerative disorders.
Cleaver's finding surprised many geneticists. The traditional view—that DNA's tightly bound double-helical structure remained stable and largely inviolable throughout the life of the cell—had already been challenged, but for the first time it was apparent that, without proper repair, propagation of cells with damaged DNA could lead to grave harm.
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Reprinted from the HHMI Bulletin,
Fall 2004, pages 50-54.
©2004 Howard Hughes Medical Institute