Richard Wood (molecular biologist)

Last updated
Richard Wood
Alma mater Westminster College
UC Berkeley
Awards FRS (1997) [1]

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

Contents

EMGS Award (2021) [6]
Scientific career
Fields DNA Repair, Mutagenesis
Institutions Yale University
ICRF
UC Berkeley
University of Pittsburgh
MD Anderson
Doctoral advisors H. John Burki
Other academic advisorsFranklin Hutchinson
Tomas Lindahl
Website Wood 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

Related Research Articles

<span class="mw-page-title-main">Molecular lesion</span> Damage to the structure of a biological molecule

A molecular lesion or point lesion is damage to the structure of a biological molecule such as DNA, RNA, or protein. This damage may result in the reduction or absence of normal function, and in rare cases the gain of a new function. Lesions in DNA may consist of breaks or other changes in chemical structure of the helix, ultimately preventing transcription. Meanwhile, lesions in proteins consist of both broken bonds and improper folding of the amino acid chain. While many nucleic acid lesions are general across DNA and RNA, some are specific to one, such as thymine dimers being found exclusively in DNA. Several cellular repair mechanisms exist, ranging from global to specific, in order to prevent lasting damage resulting from lesions.

<span class="mw-page-title-main">Xeroderma pigmentosum</span> Medical condition

Xeroderma pigmentosum (XP) is a genetic disorder in which there is a decreased ability to repair DNA damage such as that caused by ultraviolet (UV) light. Symptoms may include a severe sunburn after only a few minutes in the sun, freckling in sun-exposed areas, dry skin and changes in skin pigmentation. Nervous system problems, such as hearing loss, poor coordination, loss of intellectual function and seizures, may also occur. Complications include a high risk of skin cancer, with about half having skin cancer by age 10 without preventative efforts, and cataracts. There may be a higher risk of other cancers such as brain cancers.

<span class="mw-page-title-main">Nucleotide excision repair</span> DNA repair mechanism

Nucleotide excision repair is a DNA repair mechanism. DNA damage occurs constantly because of chemicals, radiation and other mutagens. Three excision repair pathways exist to repair single stranded DNA damage: Nucleotide excision repair (NER), base excision repair (BER), and DNA mismatch repair (MMR). While the BER pathway can recognize specific non-bulky lesions in DNA, it can correct only damaged bases that are removed by specific glycosylases. Similarly, the MMR pathway only targets mismatched Watson-Crick base pairs.

<span class="mw-page-title-main">XPB</span> Mammalian protein found in Homo sapiens

XPB is an ATP-dependent DNA helicase in humans that is a part of the TFIIH transcription factor complex.

<span class="mw-page-title-main">Pyrimidine dimer</span> Type of damage to DNA

Pyrimidine dimers represent molecular lesions originating from thymine or cytosine bases within DNA, resulting from photochemical reactions. These lesions, commonly linked to direct DNA damage, are induced by ultraviolet light (UV), particularly UVC, result in the formation of covalent bonds between adjacent nitrogenous bases along the nucleotide chain near their carbon–carbon double bonds, the photo-coupled dimers are fluorescent. Such dimerization, which can also occur in double-stranded RNA (dsRNA) involving uracil or cytosine, leads to the creation of cyclobutane pyrimidine dimers (CPDs) and 6–4 photoproducts. These pre-mutagenic lesions modify the DNA helix structure, resulting in abnormal non-canonical base pairing and, consequently, adjacent thymines or cytosines in DNA will form a cyclobutane ring when joined together and cause a distortion in the DNA. This distortion prevents DNA replication and transcription mechanisms beyond the dimerization site.

<span class="mw-page-title-main">ERCC2</span> Mammalian protein found in humans

TFIIH subunit XPD is a protein that in humans is encoded by the ERCC2 gene. It is a component of the general transcription and DNA repair factor IIH (TFIIH) core complex involved in transcription-coupled nucleotide excision repair.

Transcription factor II H (TFIIH) is an important protein complex, having roles in transcription of various protein-coding genes and DNA nucleotide excision repair (NER) pathways. TFIIH first came to light in 1989 when general transcription factor-δ or basic transcription factor 2 was characterized as an indispensable transcription factor in vitro. This factor was also isolated from yeast and finally named TFIIH in 1992.

<span class="mw-page-title-main">ERCC1</span> Protein-coding gene in the species Homo sapiens

DNA excision repair protein ERCC-1 is a protein that in humans is encoded by the ERCC1 gene. Together with ERCC4, ERCC1 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination.

<span class="mw-page-title-main">DDB2</span> Protein-coding gene in the species Homo sapiens

DNA damage-binding protein 2 is a protein that in humans is encoded by the DDB2 gene.

<span class="mw-page-title-main">RAD23B</span> Protein-coding gene in the species Homo sapiens

UV excision repair protein RAD23 homolog B is a protein that in humans is encoded by the RAD23B gene.

The enzyme DNA-(apurinic or apyrimidinic site) lyase, also referred to as DNA-(apurinic or apyrimidinic site) 5'-phosphomonoester-lyase or DNA AP lyase catalyzes the cleavage of the C-O-P bond 3' from the apurinic or apyrimidinic site in DNA via β-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate. In the 1970s, this class of enzyme was found to repair at apurinic or apyrimidinic DNA sites in E. coli and in mammalian cells. The major active enzyme of this class in bacteria, and specifically, E. coli is endonuclease type III. This enzyme is part of a family of lyases that cleave carbon-oxygen bonds.

<span class="mw-page-title-main">XPC (gene)</span> Protein-coding gene in the species Homo sapiens

Xeroderma pigmentosum, complementation group C, also known as XPC, is a protein which in humans is encoded by the XPC gene. XPC is involved in the recognition of bulky DNA adducts in nucleotide excision repair. It is located on chromosome 3.

<span class="mw-page-title-main">XPA</span> Protein-coding gene in the species Homo sapiens

DNA repair protein complementing XP-A cells is a protein that in humans is encoded by the XPA gene.

<span class="mw-page-title-main">ERCC6</span> Gene of the species Homo sapiens

DNA excision repair protein ERCC-6 is a protein that in humans is encoded by the ERCC6 gene. The ERCC6 gene is located on the long arm of chromosome 10 at position 11.23.

<span class="mw-page-title-main">ERCC5</span> Protein-coding gene in the species Homo sapiens

DNA repair protein complementing XP-G cells is a protein that in humans is encoded by the ERCC5 gene.

<span class="mw-page-title-main">ERCC4</span> Protein-coding gene in the species Homo sapiens

ERCC4 is a protein designated as DNA repair endonuclease XPF that in humans is encoded by the ERCC4 gene. Together with ERCC1, ERCC4 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination.

<span class="mw-page-title-main">ERCC8 (gene)</span> Protein-coding gene in humans

DNA excision repair protein ERCC-8 is a protein that in humans is encoded by the ERCC8 gene.

<span class="mw-page-title-main">DNA polymerase eta</span> Protein-coding gene in the species Homo sapiens

DNA polymerase eta, is a protein that in humans is encoded by the POLH gene.

<span class="mw-page-title-main">XPG N terminus</span>

In molecular biology the protein domain XPG refers to, in this case, the N-terminus of XPG. The XPG protein can be corrected by a 133 kDa nuclear protein, XPGC. XPGC is an acidic protein that confers normal ultraviolet (UV) light resistance. It is a magnesium-dependent, single-strand DNA endonuclease that makes structure-specific endonucleolytic incisions in a DNA substrate containing a duplex region and single-stranded arms. XPGC cleaves one strand of the duplex at the border with the single-stranded region.

Progeroid syndromes (PS) are a group of rare genetic disorders that mimic physiological aging, making affected individuals appear to be older than they are. The term progeroid syndrome does not necessarily imply progeria, which is a specific type of progeroid syndrome.

References

  1. 1 2 "Richard Wood, Fellow". London: Royal Society.
  2. 1 2 "Richard D. Wood EMBO profile". Heidelberg: European Molecular Biology Organization.
  3. 1 2 "Die Preisträger, Meyenburg Prize". Heidelberg: Meyenburg Stiftung. 30 April 2005.
  4. 1 2 "Elected Fellows, American Association for the Advancement of Science". Washington, D.C.: AAAS.
  5. 1 2 "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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