Richard Wood | |
|---|---|
| Alma mater | Westminster College UC Berkeley |
| Awards | FRS (1997)[1] EMBO Membership (1998)[2] |
| Scientific career | |
| Fields | DNA Repair,Mutagenesis |
| Institutions | Yale University ICRF UC Berkeley University of Pittsburgh MD Anderson |
| Doctoral advisors | H. John Burki |
| Other academic advisors | Franklin Hutchinson Tomas Lindahl |
| Website | Wood Laboratory |
Richard D. Wood (born June 3, 1955 inBoulder, Colorado) is an American molecular biologist specializing in research onDNA repair andmutation.[7] He is known for pioneering studies onnucleotide excision repair (NER), particularly for reconstituting the minimum set of proteins involved in this process,[8][9] identifying proliferating cell nuclear antigen (PCNA)[10] as part of the NER complex and identifying mammalian repairpolymerases.[11][12]
The NER DNA repair pathway is a complex mechanism that cells use to repair DNA damage caused by ultraviolet sun exposure. The pathway is essential to life, and children born with mutations in genes coding for NER proteins developxeroderma pigmentosum or XP. XP patients cannot repair DNA mutations, particularlypyrimidine dimers, caused byUV and must be continuously protected from sunlight to prevent fatal skin scarring and cancers. By the 1980s, scientists (notablyAziz Sancar) had uncovered how NER works in bacteria but this pathway remained poorly understood in mammalian cells.
Wood's first breakthrough came in 1988, after he moved to England to work at theImperial Cancer Research Fund withTomas Lindahl (Lindahl, Sancar andPaul Modrich later would receive the 2015Nobel Prize in Chemistry for their contributions to DNA repair). Working in Lindahl's lab, Wood developed a way to perform NER on DNA in a test tube using crude cell-free extracts from tissues.[13] By performing this test on extracts derived from blood cells of children with XP, Wood could begin deciphering which different proteins are involved in the NER process. Extracts from group A XP cells, for example, could be “complemented” to resume DNA repair by adding cellular extracts obtained from group C XP patients (who have a normal group A protein but a non-functional group C protein).
Wood established his own group at ICRF and over the next decade, performed a series of biochemistry experiments to understand each step in the repair process by adding individual, purified proteins.[14] Repair (particularly of UV-inducedpyrimidine dimers) includes recognition of the damaged site (probably by sensing an unpaired bubble at the mutation site), nicking the DNA at upstream and downstream sites, excising the damaged DNA, then filling in the single-stranded DNA gap using apolymerase, with the opposite strand serving as a template for the proper sequence for the repair patch. Since multiple proteins are involved in NER, different XP patients may have different gene mutations (called "complementation groups" based on which enzyme is defective in the NER pathway). Ultimately, his group showed that the entire NER pathway could be performed synthetically by reconstituting 30 different purified proteins, allowing him to define DNA repair at the molecular level.[15] Since returning to the United States, his laboratory has focused on the role polymerases play in making ‘emergency’ translesion repairs that lead to additional mutational errors and contribute to cancers.[16]
Wood received hisB.S. degree inBiology fromWestminster College, Salt Lake CityUtah (1977), hisPh.D. degree inBiophysics at theUniversity of California, Berkeley (1981), and was apostdoctoral fellow atYale University from 1982 to 1985. He currently is J. Ralph Meadows Professor in Carcinogenesis at theUniversity of Texas MD Anderson Cancer Center[17] and was elected to the USNational Academy of Sciences in 2023. He is a jazz bassist (he was a college roommate of the Hollywood composer and orchestratorGeoff Stradling) and plays in local bands and together with his wife Enid Wood, a violinist and artist.[18]
