DNA damage and repair

摘要

This retrospective reflection by Francis Crick, penned two decades after he and James Watson reported the structure of DNA, hints at the early perception of DNA as a highly stable macromolecular entity. This prevailing view at the time significantly delayed serious consideration of biochemical processes such as mutation and repair. It was once suggested by Frank Stahl that "the possibility that... genes were ... subject to the hurly-burly of both insult and clumsy efforts to reverse the insults, was unthinkable." But subsequent work on three 'R's' of DNA metabolism― replication (copying of DNA prior to each cell division), recombination (exchanges between different DNA molecules in a cell) and repair (restoration of altered DNA to its normal state)―revealed the dynamic state of DNA. It became apparent that DNA in all living organisms continually incurs a myriad of types of damage, and that cells have devised ingenious mechanisms for tolerating and repairing the damage. Failure of these mechanisms can lead to serious disease consequences, as well illustrated in the human hereditary diseases xeroderma pigmentosum (XP), hereditary non-polyposis colon cancer (HNPCC) and some forms of breast cancer. XP is characterized by about a 10,000-fold increased risk of skin cancer associated with sunlight exposure; individuals with HNPCC manifest an increased hereditary predisposition to colon (and other) cancer.