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Richard Wood (molecular biologist)

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Richard Wood
Alma materWestminster College
UC Berkeley
AwardsFRS (1997)[1]

EMBO Membership (1998)[2]
Meyenburg Prize (1998)[3]
Fellow AAAS (2013)[4]
Fellow Am. Acad Arts & Sci (2018)[5]

EMGS Award (2021)[6]
Scientific career
FieldsDNA Repair, Mutagenesis
InstitutionsYale University
ICRF
UC Berkeley
University of Pittsburgh
MD Anderson
Doctoral advisorsH. John Burki
Other academic advisorsFranklin Hutchinson
Tomas Lindahl
WebsiteWood Laboratory

Richard D. Wood (born June 3, 1955 in Boulder, Colorado) is an American molecular biologist specializing in research on DNA repair and mutation.[7] He is known for pioneering studies on nucleotide 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 repair polymerases.[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 develop xeroderma pigmentosum or XP. XP patients cannot repair DNA mutations, particularly pyrimidine dimers, caused by UV and must be continuously protected from sunlight to prevent fatal skin scarring and cancers. By the 1980s, scientists (notably Aziz 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 the Imperial Cancer Research Fund with Tomas Lindahl (Lindahl, Sancar and Paul Modrich later would receive the 2015 Nobel 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-induced pyrimidine 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 a polymerase, 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 his B.S. degree in Biology from Westminster College, Salt Lake City Utah (1977), his Ph.D. degree in Biophysics at the University of California, Berkeley (1981), and was a postdoctoral fellow at Yale University from 1982 to 1985. He currently is J. Ralph Meadows Professor in Carcinogenesis at the University of Texas MD Anderson Cancer Center[17] and was elected to the US National Academy of Sciences in 2023. He is a jazz bassist (he was a college roommate of the Hollywood composer and orchestrator Geoff Stradling) and plays in local bands and together with his wife Enid Wood, a violinist and artist.[18]

Awards

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References

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  1. ^ a b "Richard Wood, Fellow". London: Royal Society.
  2. ^ a b "Richard D. Wood EMBO profile". Heidelberg: European Molecular Biology Organization.
  3. ^ a b "Die Preisträger, Meyenburg Prize". Heidelberg: Meyenburg Stiftung. 30 April 2005.
  4. ^ a b "Elected Fellows, American Association for the Advancement of Science". Washington, D.C.: AAAS.
  5. ^ a b "Dr. Richard D. Wood". Cambridge, Mass: American_Academy of Arts and Sciences.
  6. ^ "EMGS Award". Jacksonville, FL: Environmental Mutagenesis and Genomics Society.
  7. ^ Lindahl, T. (1999). "Quality Control by DNA Repair". Science. 286 (5446). Science 1999:286;1897-1905: 1897–1905. doi:10.1126/science.286.5446.1897. PMID 10583946.
  8. ^ Aboussekhra, Abdelilah; Biggerstaff, Maureen; Shivji, Mahmud K.K; Vilpo, Juhani A; Moncollin, Vincent; Podust, Vladimir N; Protić, Miroslava; Hübscher, Ulrich; Egly, Jean-Marc; Wood, Richard D (1995). "Mammalian DNA nucleotide excision repair reconstituted with purified protein components". Cell. 80 (6): 859–868. doi:10.1016/0092-8674(95)90289-9. PMID 7697716.
  9. ^ Araújo, SJ; Tirode, F; Coin, F; et al. (February 2000). "Nucleotide excision repair of DNA with recombinant human proteins: definition of the minimal set of factors, active forms of TFIIH, and modulation by CAK". Genes Dev. 14 (3): 349–59. doi:10.1101/gad.14.3.349. PMC 316364. PMID 10673506.
  10. ^ Shivji, Mahmud K.K. (1992). "Proliferating cell nuclear antigen is required for DNA excision repair". Cell. 69 (2): 367–374. doi:10.1016/0092-8674(92)90416-A. PMID 1348971. S2CID 12260457.
  11. ^ Marini, Federica; Kim, Nayun; Schuffert, Anthony; Wood, Richard D. (2003). "POLN, a Nuclear PolA Family DNA Polymerase Homologous to the DNA Cross-link Sensitivity Protein Mus308". Journal of Biological Chemistry. 278 (34): 32014–32019. doi:10.1074/jbc.M305646200. PMID 12794064.
  12. ^ Seki, M.; Marini, F.; Wood, R. D. (2003). "POLQ (Pol θ), a DNA polymerase and DNA‐dependent ATPase in human cells". Nucleic Acids Research. 31 (21): 6117–6126. doi:10.1093/nar/gkg814. PMC 275456. PMID 14576298.
  13. ^ Wood, RD; Robins, P; Lindahl, T (1988). "Complementation of the xeroderma pigmentosum DNA repair defect in cell-free extracts". Cell. 53 (1): 97–106. doi:10.1016/0092-8674(88)90491-6. PMID 3349527. S2CID 9810684.
  14. ^ Robins, P; Jones, CJ; Biggerstaff, M; Lindahl, T; Wood, RD (1991). "Complementation of DNA repair in xeroderma pigmentosum group A cell extracts by a protein with affinity for damaged DNA". EMBO Journal. 10 (12): 3913–21. doi:10.1002/j.1460-2075.1991.tb04961.x. PMC 453130. PMID 1935910.
  15. ^ Aboussekhra, Abdelilah; Biggerstaff, Maureen; Shivji, Mahmud K.K; Vilpo, Juhani A.; Moncollin, Vincent; Podust, Vladimir N.; Protić, Miroslava; Hübscher, Ulrich; Egly, Jean-Marc; Wood, Richard D. (1995). "Mammalian DNA nucleotide excision repair reconstituted with purified protein components". Cell. 80 (6): 859–868. doi:10.1016/0092-8674(95)90289-9. PMID 7697716.
  16. ^ Lange, SS; Takata, K; Wood, RD (2011). "DNA polymerases and cancer". Nat Rev Cancer. 11 (2): 96–110. doi:10.1038/nrc2998. PMC 3739438. PMID 21258395.
  17. ^ "Richard D. Wood, Ph.D.: Professor". Retrieved 13 August 2022.
  18. ^ "Enid A. Wood Fine Art". Retrieved 14 August 2022.
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