Early days of DNA repair: discovery of nucleotide excision repair and homology-dependent recombinational repair

Abstract

The discovery of nucleotide excision repair in 1964 showed that DNA could be repaired by a mechanism that removed the damaged section of a strand and replaced it accurately by using the remaining intact strand as the template. This result showed that DNA could be actively metabolized in a process that had no precedent. In 1968, experiments describing postreplication repair, a process dependent on homologous recombination, were reported. The authors of these papers were either at Yale University or had prior Yale connections. Here we recount some of the events leading to these discoveries and consider the impact on further research at Yale and elsewhere.

Keywords: DNA repair; Yale Radiobiology; homology-dependent repair; leading strand restart; nucleotide excision repair; recombination; recombinational repair.

Figure 1

Abbreviated lineage of several researchers in the Radiobiology Section at Yale University during the first decade. Paul Howard-Flanders formed the Radiobiology Section when he came to Yale in 1959. Postdoctoral associates who were in his lab before or during the discovery of NER in 1964 included Jane Setlow, Boyce, Emmerson, and Johansen. Rupp joined the Howard-Flanders lab as a postdoc a few months after the discovery of NER. In 1968, Summers and Low came to Yale as junior faculty members with independent labs. Solid lines (without arrows) indicate that one individual worked in another lab. Lines with arrows indicate movement either to or from Yale. Although not shown, Seeberg (1 year) and Strike (6 months) were both in the Rupp lab and later collaborated with each other as described in the text. Another interaction not shown in the figure is between West and Lloyd, who did important studies on the resolution of Holliday junctions. Ian Hickson, who did his predoctoral work in Emmerson’s lab, is the only person in this diagram who did not work at Yale.