Charles Clifton Richardson (born May 7, 1935) is an American biochemist and professor at

Harvard University Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...

. Richardson received his undergraduate education at

Duke University Duke University is a private research university in Durham, North Carolina. Founded by Methodists and Quakers in the present-day city of Trinity in 1838, the school moved to Durham in 1892. In 1924, tobacco and electric power industrialist James ...

, 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 Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consi ...

, and he served as editor/associate editor of the ''

Annual Review of Biochemistry ''Annual Review of Biochemistry'' is an annual peer reviewed scientific journal published by Annual Reviews, a nonprofit scientific publisher. Its first volume was published in 1932, and its founding editor was J. Murray Luck. The current editor ...

'' from 1972 to 2003. Richardson received the

American Chemical Society The American Chemical Society (ACS) is a scientific society based in the United States that supports scientific inquiry in the field of chemistry. Founded in 1876 at New York University, the ACS currently has more than 155,000 members at all d ...

Award in Biological Chemistry in 1968, as well as numerous other accolades.

Early life and education

Charles Richardson was born on May 7, 1935, in

Wilson, North Carolina Wilson is a city in and the county seat of Wilson County, North Carolina, United States. Located approximately east of the capital city of Raleigh, it is served by the interchange of Interstate 95 and U.S. Route 264. Wilson had an estimated p ...

. 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 Columbia is the capital of the U.S. state of South Carolina. With a population of 136,632 at the 2020 census, it is the second-largest city in South Carolina. The city serves as the county seat of Richland County, and a portion of the city ...

. Richardson graduated from

Dreher High School Dreher High School is a co-educational four-year public high school in Richland County School District One located in Columbia, South Carolina, United States. Dreher, established in 1938, is one of the oldest public high schools in South Carolina ...

and received a full scholarship to

in 1953. Without completing a bachelor's degree, Richardson enrolled in Duke Medical School in 1956. In 1959, Richardson completed a

Bachelor of Science A Bachelor of Science (BS, BSc, SB, or ScB; from the Latin ') is a bachelor's degree awarded for programs that generally last three to five years. The first university to admit a student to the degree of Bachelor of Science was the University of ...

degree in medicine from Duke through the

National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...

(NIH)

United States Public Health Service The United States Public Health Service (USPHS or PHS) is a collection of agencies of the Department of Health and Human Services concerned with public health, containing nine out of the department's twelve operating divisions. The Assistant S ...

Post-Sophomore Research Fellowship. Richardson graduated from Duke Medical School and began residency at

Duke University Hospital Duke University Hospital is a 957-acute care bed academic tertiary care facility located in Durham, North Carolina. Established in 1930, it is the flagship teaching hospital for the Duke University Health System, a network of physicians and hos ...

in 1960. On July 29, 1961, Richardson married Ingrid Hanssum at the Gothic Duke Chapel. They have two children.

Career and research

In 1961, Richardson obtained a

Public Health Service In public relations and communication science, publics are groups of individual people, and the public (a.k.a. the general public) is the totality of such groupings. This is a different concept to the sociological concept of the ''Öffentlichkei ...

fellowship under

Arthur Kornberg Arthur Kornberg (March 3, 1918 – October 26, 2007) was an American biochemist who won the Nobel Prize in Physiology or Medicine 1959 for the discovery of "the mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic ac ...

in his biochemistry laboratory at

Stanford Medical School Stanford University School of Medicine is the medical school of Stanford University and is located in Stanford, California. It traces its roots to the Medical Department of the University of the Pacific, founded in San Francisco in 1858. This ...

. As a result, Richardson and Ingrid Hanssum moved to

Palo Alto Palo Alto (; Spanish for "tall stick") is a charter city in the northwestern corner of Santa Clara County, California, United States, in the San Francisco Bay Area, named after a coastal redwood tree known as El Palo Alto. The city was estab ...

. In Kornberg's lab, Richardson focused on improving the purification technique of

DNA polymerase A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create ...

from '' E. coli''. In Kornberg's lab, Richardson worked alongside

Paul Berg Paul Berg (born June 30, 1926) is an American biochemist and professor emeritus at Stanford University. He was the recipient of the Nobel Prize in Chemistry in 1980, along with Walter Gilbert and Frederick Sanger. The award recognized their con ...

, Reiji and Tsunko Okazaki, and several others. In 1964, Richardson left Kornberg's lab and began a faculty position at

, where he was promoted to tenure in 1967. Richardson served as chairman of the department of

biological chemistry Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...

from 1978 to 1987. Additionally, Richardson served as editor or associate editor of the ''

'' from 1972 to 2003. As of 2020, Richardson continues his position as professor at Harvard Medical School. Richardson taught four doctoral students: Dennis M. Livingston, David N. Frick, Richard D. Colodner, and Paul L. Modrich. Throughout Richardson's career, Richardson used

bacteriophage A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bacteri ...

s in order to investigate

DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritanc ...

. Richardson discovered and researched several enzymes throughout his career: ''E. coli'' exonuclease III in 1964, T4 DNA ligase in 1967,

T7 DNA polymerase T7 DNA polymerase is an enzyme used during the DNA replication of the T7 bacteriophage. During this process, the DNA polymerase “reads” existing DNA strands and creates two new strands that match the existing ones. The T7 DNA polymerase require ...

in 1971, ''E. coli'' exonuclease VII in 1974, ''E. coli'' DNA polymerase III in 1975, T4 polynucleotide kinase in 1981, T7 DNA primase in the late 1980s and early 1990s, and T7 DNA helicase in 2004. Richardson used these enzymes to further analyze DNA, develop sequencing reagents, and characterize the mechanisms of DNA replication. Richardson's most highly-cited accomplishment was made while working with bacteriophage

T7 RNA polymerase T7 RNA Polymerase is an RNA polymerase from the T7 bacteriophage that catalyzes the formation of RNA from DNA in the 5'→ 3' direction. Activity T7 polymerase is extremely promoter-specific and transcribes only DNA downstream of a T7 promo ...

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. 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 Thioredoxin is a class of small redox proteins known to be present in all organisms. It plays a role in many important biological processes, including redox signaling. In humans, thioredoxins are encoded by ''TXN'' and '' TXN2'' genes. Loss-of-fu ...

at a one-to-one stoichiometric ratio. 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 In molecular biology, a hybridization probe (HP) is a fragment of DNA or RNA of usually 15–10000 nucleotide long which can be radioactively or fluorescently labeled. HP can be used to detect the presence of nucleotide sequences in analyzed RN ...

, and lack of background pause sites and uniform distribution of dideoxy-terminated fragments. In 1998, Richardson examined the

crystal structure In crystallography, crystal structure is a description of the ordered arrangement of atoms, ions or molecules in a crystal, crystalline material. Ordered structures occur from the intrinsic nature of the constituent particles to form symmetric pat ...

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 A nucleoside triphosphate is a nucleoside containing a nitrogenous base bound to a 5-carbon sugar (either ribose or deoxyribose), with three phosphate groups bound to the sugar. They are the molecular precursors of both DNA and RNA, which are cha ...

in the polymerase

active site In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) a ...

. 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 {{unreferenced, date=May 2015 A phosphoryl group is the chemical ion or radical: P+O32−, containing phosphorus and oxygen. (The correct chemical name for this −PO32− group is phosphonato, and phosphono for −PO3H2; as ''phosphoryl'' in ch ...

transfer by related polymerases with metal. More recently in 2011, Richardson developed a single-molecule assay to measure the activity of the

replisome The replisome is a complex molecular machine that carries out replication of DNA. The replisome first unwinds double stranded DNA into two single strands. For each of the resulting single strands, a new complementary sequence of DNA is synt ...

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.

Awards and honors

* National Institutes of Health (NIH)

Post-Sophomore Research Fellowship, 1958–1959 * Career Development Award,

, 1967–1976 *

Award in Biological Chemistry, sponsored by Eli Lily & Co., 1968 * Duke Medical Center Alumni Award, 1972 *

MERIT award, 1986–1995 *

American Society for Biochemistry and Molecular Biology The American Society for Biochemistry and Molecular Biology (ASBMB) is a learned society that was founded on December 26, 1906, at a meeting organized by John Jacob Abel (Johns Hopkins University). The roots of the society were in the American Phy ...

-Merck * Award in Biochemistry and Molecular Biology, 1996 * Herbert Tabor/

Journal of Biological Chemistry The ''Journal of Biological Chemistry'' (''JBC'') is a weekly peer-reviewed scientific journal that was established in 1905., jbc.org Since 1925, it is published by the American Society for Biochemistry and Molecular Biology. It covers research in ...

Lectureship Award, 2006 * Weinhouse 2007 Lecturer,

Thomas Jefferson University Thomas Jefferson University is a private research university in Philadelphia, Pennsylvania. Established in its earliest form in 1824, the university officially combined with Philadelphia University in 2017. To signify its heritage, the univer ...

Memberships

Phi Beta Kappa The Phi Beta Kappa Society () is the oldest academic honor society in the United States, and the most prestigious, due in part to its long history and academic selectivity. Phi Beta Kappa aims to promote and advocate excellence in the liberal a ...

Alpha Omega Alpha Alpha Omega Alpha Honor Medical Society () is an honor society in the field of medicine. Alpha Omega Alpha currently has active Chapters in 132 LCME- accredited medical schools in the United States and Lebanon. It annually elects over 4,000 new ...

Pi Mu Epsilon Pi Mu Epsilon ( or ) is the U.S. honorary national mathematics society. The society was founded at Syracuse University on , by Professor Edward Drake Roe, Jr, and currently has chapters at 371 institutions across the US. Goals Pi Mu Epsilon is d ...

A.M. (Hon),

, 1967 * Elected Fellow,

American Academy of Arts and Sciences The American Academy of Arts and Sciences (abbreviation: AAA&S) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, and ...

, 1975 * Elected Member,

National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nati ...

, 1983 * Elected Member,

Institute of Medicine The National Academy of Medicine (NAM), formerly called the Institute of Medicine (IoM) until 2015, is an American nonprofit, non-governmental organization. The National Academy of Medicine is a part of the National Academies of Sciences, E ...

, 1986

References

External links