Charles C. Richardson

Charles Clifton Richardson (born May 7, 1935) is an American biochemist and professor at Harvard University. Richardson received his undergraduate education at Duke University, where he majored in medicine. He received his M.D. at Duke Medical School in 1960. Richardson works as a professor at Harvard Medical School, and he served as editor/associate editor of the Annual Review of Biochemistry from 1972 to 2003.[1] Richardson received the American Chemical Society Award in Biological Chemistry in 1968, as well as numerous other accolades.[2]

Charles C. Richardson
Born(1935-05-07)May 7, 1935
Wilson, NC, United States
Alma materDuke Medical School
Duke University
Spouse(s)Ingrid Hanssum (1961; 2 children)
Scientific career
FieldsMolecular biology
InstitutionsHarvard University

Early life and education

Charles Richardson was born on May 7, 1935, in Wilson, North Carolina.[1] His father, Barney Clifton Richardson, was an accountant at a local automobile dealership. His mother, Elizabeth Barefoot, was a housewife. At 11 years old, Richardson and his family moved to Columbia, South Carolina. Richardson graduated from Dreher High School and received a full scholarship to Duke University in 1953. Without completing a bachelor's degree, Richardson enrolled in Duke Medical School in 1956. In 1959, Richardson completed a Bachelor of Science degree in medicine from Duke through the National Institutes of Health (NIH) United States Public Health Service Post-Sophomore Research Fellowship. Richardson graduated from Duke Medical School and began residency at Duke University Hospital in 1960. On July 29, 1961, Richardson married Ingrid Hanssum at the Gothic Duke Chapel. They have two children.[1]

Career and research

In 1961, Richardson obtained a Public Health Service fellowship under Arthur Kornberg in his biochemistry laboratory at Stanford Medical School. As a result, Richardson and Ingrid Hanssum moved to Palo Alto. In Kornberg's lab, Richardson focused on improving the purification technique of DNA polymerase from E. coli. In Kornberg's lab, Richardson worked alongside Paul Berg, Reiji and Tsunko Okazaki, and several others. In 1964, Richardson left Kornberg's lab and began a faculty position at Harvard Medical School, where he was promoted to tenure in 1967. Richardson served as Chairman of the department of biological chemistry from 1978 to 1987. Additionally, Richardson served as editor or associate editor of the Annual Review of Biochemistry from 1972 to 2003. As of 2020, Richardson continues his position as professor at Harvard Medical School.[1] Richardson taught four doctoral students: Dennis M. Livingston, David N. Frick, Richard D. Colodner, and Paul L. Modrich.[3]

Throughout Richardson's career, Richardson used bacteriophages in order to investigate DNA replication. Richardson discovered and researched several enzymes throughout his career: E. coli exonuclease III[4] in 1964, T4 DNA ligase[5] in 1967, T7 DNA polymerase[6] in 1971, E. coli exonuclease VII[7][8] in 1974, E. coli DNA polymerase III[9][10] in 1975, T4 polynucleotide kinase[11] in 1981, T7 DNA primase[12][13] in the late 1980s and early 1990s, and T7 DNA helicase[14] in 2004. Richardson used these enzymes to further analyze DNA, develop sequencing reagents, and characterize the mechanisms of DNA replication.[15]

Richardson's most highly-cited accomplishment was made while working with bacteriophage T7 RNA polymerase in 1985. Richardson used the T7 RNA polymerase/promoter system to control the expression of a phage T7 gene 5 protein (gp5), which is a subunit of T7 DNA polymerase. By combining the specificity of T7 RNA polymerase for its own promoters with rifampicin's ability to selectively inhibit the host RNA polymerase, Richardson established a method to exclusively express genes, specifically the phage T7 gene 5 protein, under the control of the T7 RNA polymerase promoter. During this process, Richardson constructed a T7 phage with deletions in gene 1 that propagate in E. coli cells expressing T7 RNA polymerase. Richardson proposed the T7 RNA polymerase/promoter system as an "attractive alternative" to the mini- or maxicell.[16]

A couple years later, Richardson researched a self-made DNA polymerase for potential use in DNA sequencing. This highly processive DNA polymerase was composed of an 84-kDa T7 gene 5 protein and 12-kDa E. coli thioredoxin at a one-to-one stoichiometric ratio.[17] In his study, Richardson demonstrated that this modified DNA polymerase would be ideal for DNA sequencing by the chain-termination method. Richardson based this finding off of three main factors: high processivity and lack of associated exonuclease activity, ability to use low concentrations of radioactive nucleotides for preparation of DNA probes, and lack of background pause sites and uniform distribution of dideoxy-terminated fragments.[18]

In 1998, Richardson examined the crystal structure of a bacteriophage T7 DNA replication complex at 2.2 Å resolution. Before imaging, Richardson complexed the T7 bacteriophage DNA polymerase with a primer-template and a nucleoside triphosphate in the polymerase active site. Through analysis of the crystal structure, Richardson determined how the replication complex selects nucleotides in a template-directed manner. Furthermore, Richardson established an understanding of the basis for phosphoryl transfer by related polymerases with metal.[19]

More recently in 2011, Richardson developed a single-molecule assay to measure the activity of the replisome with fluorescently-labeled DNA polymerases. Richardson then used this assay to quantify the process of polymerase exchange. Richardson determined that soluble polymerases are recruited to an actively synthesizing replisome, which leads to a polymerase exchange event between the excess polymerases and the synthesizing polymerase after about 50 seconds. This supports the belief that replisomes are highly dynamic complexes.[20]

Awards and honors

Memberships

References
  1. Richardson, Charles C. (June 2, 2015). "It Seems Like Only Yesterday". Annual Review of Biochemistry. 84 (1): 1–34. doi:10.1146/annurev-biochem-060614-033850. ISSN 0066-4154. PMID 26034887.
  2. Richardson, Charles. "Curriculum Vitae". Charles C. Richardson Laboratory. Retrieved March 8, 2020.
  3. "Chemistry Tree - Charles C. Richardson Family Tree". academictree.org. Retrieved April 19, 2020.
  4. Richardson, Charles C.; Lehman, I. R.; Kornberg, Arthur (January 1, 1964). "A Deoxyribonucleic Acid Phosphatase-Exonuclease from Escherichia coli II. Characterization of the Exonuclease Activity". Journal of Biological Chemistry. 239 (1): 251–258. ISSN 0021-9258. PMID 14114851.
  5. Fareed, G C; Richardson, C C (1967). "Enzymatic breakage and joining of deoxyribonucleic acid. II. The structural gene for polynucleotide ligase in bacteriophage T4". Proceedings of the National Academy of Sciences of the United States of America. 58 (2): 665–672. Bibcode:1967PNAS...58..665F. doi:10.1073/pnas.58.2.665. ISSN 0027-8424. PMC 335686. PMID 5234326.
  6. Grippo, Pasquale; Richardson, Charles C. (November 25, 1971). "Deoxyribonucleic Acid Polymerase of Bacteriophage T7". Journal of Biological Chemistry. 246 (22): 6867–6873. ISSN 0021-9258. PMID 4942327.
  7. Chase, John W.; Richardson, Charles C. (July 25, 1974). "Exonuclease VII of Escherichia coli Purification and Properties". Journal of Biological Chemistry. 249 (14): 4545–4552. ISSN 0021-9258. PMID 4602029.
  8. Chase, John W.; Richardson, Charles C. (July 25, 1974). "Exonuclease VII of Escherichia coli Mechanism of Action". Journal of Biological Chemistry. 249 (14): 4553–4561. ISSN 0021-9258. PMID 4602030.
  9. Livingston, D. M.; Hinkle, D. C.; Richardson, C. C. (January 25, 1975). "Deoxyribonucleic acid polymerase III of Escherichia coli. Purification and properties". Journal of Biological Chemistry. 250 (2): 461–469. ISSN 0021-9258. PMID 1089643.
  10. Livingston, D. M.; Richardson, C. C. (January 25, 1975). "Deoxyribonucleic acid polymerase III of Escherichia coli. Characterization of associated exonuclease activities". Journal of Biological Chemistry. 250 (2): 470–478. ISSN 0021-9258. PMID 163228.
  11. Richardson, Charles C. (January 1, 1981), Boyer, Paul D. (ed.), 16 Bacteriophage T4 Polynucleotide Kinase, The Enzymes, 14, Academic Press, pp. 299–314, doi:10.1016/S1874-6047(08)60342-X, ISBN 9780121227142, retrieved April 17, 2020
  12. Bernstein, J. A.; Richardson, C. C. (August 5, 1989). "Characterization of the helicase and primase activities of the 63-kDa component of the bacteriophage T7 gene 4 protein". Journal of Biological Chemistry. 264 (22): 13066–13073. ISSN 0021-9258. PMID 2546945.
  13. Mendelman, L. V.; Notarnicola, S. M.; Richardson, C. C. (December 25, 1993). "Evidence for distinct primase and helicase domains in the 63-kDa gene 4 protein of bacteriophage T7. Characterization of nucleotide binding site mutant". Journal of Biological Chemistry. 268 (36): 27208–27213. ISSN 0021-9258. PMID 8262962.
  14. Crampton, Donald J.; Richardson, Charles C. (January 1, 2003). "Bacteriophage T7 gene 4 protein: A hexameric DNA helicase". In Hackney, David D.; Tamanoi, Fuyuhiko (eds.). Energy Coupling and Molecular Motors. The Enzymes. Energy Coupling and Molecular Motors. 23. Academic Press. pp. 277–302. doi:10.1016/S1874-6047(04)80007-6. ISBN 9780121227241. Retrieved April 17, 2020.
  15. Kresge, Nicole; Simoni, Robert D.; Hill, Robert L. (July 13, 2007). "DNA Replication in Bacteriophage: the Work of Charles C. Richardson". Journal of Biological Chemistry. 282 (28): e22. ISSN 0021-9258.
  16. Tabor, S.; Richardson, C. C. (February 1, 1985). "A bacteriophage T7 RNA polymerase/promoter system for controlled exclusive expression of specific genes". Proceedings of the National Academy of Sciences. 82 (4): 1074–1078. Bibcode:1985PNAS...82.1074T. doi:10.1073/pnas.82.4.1074. ISSN 0027-8424. PMC 397196. PMID 3156376.
  17. Mark, D. F.; Richardson, C. C. (March 1, 1976). "Escherichia coli thioredoxin: a subunit of bacteriophage T7 DNA polymerase". Proceedings of the National Academy of Sciences. 73 (3): 780–784. Bibcode:1976PNAS...73..780M. doi:10.1073/pnas.73.3.780. ISSN 0027-8424. PMC 336002. PMID 768986.
  18. Tabor, S.; Richardson, C. C. (July 1, 1987). "DNA sequence analysis with a modified bacteriophage T7 DNA polymerase". Proceedings of the National Academy of Sciences. 84 (14): 4767–4771. Bibcode:1987PNAS...84.4767T. doi:10.1073/pnas.84.14.4767. ISSN 0027-8424. PMC 305186. PMID 3474623.
  19. Doublié, Sylvie; Tabor, Stanley; Long, Alexander M.; Richardson, Charles C.; Ellenberger, Tom (1998). "Crystal structure of a bacteriophage T7 DNA replication complex at 2.2 Å resolution". Nature. 391 (6664): 251–258. Bibcode:1998Natur.391..251D. doi:10.1038/34593. ISSN 1476-4687. PMID 9440688. S2CID 4384241.
  20. Loparo, Joseph J.; Kulczyk, Arkadiusz W.; Richardson, Charles C.; van Oijen, Antoine M. (January 18, 2011). "Simultaneous single-molecule measurements of phage T7 replisome composition and function reveal the mechanism of polymerase exchange". Proceedings of the National Academy of Sciences. 108 (9): 3584–3589. doi:10.1073/pnas.1018824108. ISSN 0027-8424. PMC 3048139. PMID 21245349.

Further reading
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