Citation | R.D. Wood is influential for his work on DNA repair and mutagenesis, which creatively combines genetics, molecular biology, and biochemistry. In early studies he explored the cell-cycle related rsponse to radiation of DNA repair-deficient mammalian cells, and constructed a comprehensive picture of the DNA sequence changes caused by ultraviolet light. His most important breakthrough was to find a way to achieve nucleotide excision repair of DNA with human proteins in a cell-free system. This led to isolation of the XPA protein (defective in individuals with the cancer-prone inherited syndrome xeroderma pigmentosum) and the discovery that XPA preferentially binds to DNA damage. Dissection of the cell-free system also revealed that the DNA single-stranded binding protein RPA was required for incision of damaged DNA, and the DNA polymerase accessory factor PCNA for DNA repair synthesis. Work in Wood's laboratory elucidated the mechanism of the dual incision reaction of necleotide excision repair. The XPG nuclease and the ERCC1-XPF nuclease were found to be unusual enzymes that recognize and specifically cut branched DNA structures with opposite polarities. The entire nucleotide excision repair reaction was recently reconstituted with purified proteins, setting a landmark in the field and paving the way for further fundamental discoveries concerning the mechanism of DNA repair. |