DNA repair and evolutionary considerations. A search for a general principle in nuclear biology with use of radiation as a probe.

Three types of DNA repair are known: photoenzymatic repair, excision repair, and tolerance repair (the ability to generate damage-free copies of DNA, which could be not exact copies, from damaged DNA templates). Photoenzymatic repair involves the most simple molecular mechanisms and is the most specific (effective only for pyrimidine dimers) and the most widely distributed among present living organisms, followed by excision repair and then by tolerance repair in order of increasing complexity. It is proposed that these repair systems also evolved in this order after the primordial life was created by solar UV light. Current but fragmentary evidence concerning the molecular and genetic bases of the three types of repair tends to support the idea that the increase in DNA-content needed for the evolution of higher forms from the prokaryotes may have been accompanied by the inherent threat of fragility of the giant DNA molecules, so that the higher forms now possess a greatly increased tolerance capacity. Probably the increase is approximately proportional to their DNA content compared with that of prokaryotes. It is shown theoretically that photoenzymatic and excision repair alone cannot deal with the inherent fragility of giant DNA. The development of tolerance-repair capacity, however, inevitably enhances probability of errors in the repair of DNA damage, leading to the accumulation of misrepair events such as mutation, chromosomal aberration and cancer. It is proposed that DNA repair and misreplication repair are responsible for preventing living organisms from regressing to the randomness-dominated world of the non-living. Living organisms would have evolved slowly along zigzag lines between error and repair of DNA.