Meselson

The mechanism of strand-directed mismatch correction has been demonstrated in E. coli (see, e.g., Wagner and Meselson, 1976). In this organism, adenine methyla-tion of d(G-A-T-C) sequences determines the strand on which repair occurs. Thus, parental DNA is fully methylated, while newly synthesized DNA is undermethylated, for a period sufficient for mismatch correction. By this means the organism preserves the presumed correct sequence, i.e., that present on the original DNA strand, and removes the aberrant base on the newly synthesized strand. Adenine methylation is achieved in E. coli by the dam methylase, which is dependent on S-adenosylmethionine. Mutants (dam) lacking this methylase are hypermutable, as would be expected by this model (Marinus and Morris, 1974). 

In addition, Meselson was a member of the NAE Committee on Alternative Chemical Demilitarization Technologies and the Advisory Panel on the Chemical Research, Development and Engineering Center. I decided to write to him, and composed a two-page letter pointing out that he and I were approximately the same age, and had similar Ivy League educations. I wondered why we had reached such different views on the topic of chemical warfare, especially about incapacitating agents, which were intended to reduce wartime casualties. 

Dr. Meselson remains a prominent leader in the cause of arms control, especially biological and chemical weapons, and has been the recipient of many deserved awards. It was nice that, despite our ideological differences, we were able to have a frank and friendly (although brief) exchange of opinions. 

Earlier, we did a thonght experiment abont one way that DNA replication could take place. In this mechanism, termed semiconservative, each new strand of DNAis paired with one of the old strands that is, the two strands of the original DNA molecule are now divided between the two molecnles, each of which has one old strand and one new strand. However, there is another possibility, termed conservative. In this case, the two new strands are paired with each other and the two old strands remain paired with each other. Matthew Meselson and W. F. Stahl provided compelling evidence that DNA replication is semiconservative. Here is how the experiment was done. ... 

The Meselson-Stahl experiment is described in M. Meselson and F. W. Stahl, ProcNatl AcadSci USA 44 671-682 (1958). 

Meselson, M. and Russell, K., Comparisons of Carcinogenic and Mutagenic Potency, in Origins of Human Cancer (see ref. 1 for citation). 

As the field of molecular genetics grew, the DNA molecule became the focus of many research efforts. Francis Crick and George Gamov developed the sequence hypothesis to explain how DNA makes protein. They stated that the DNA sequence specifies the amino acid sequence of a protein and postulated the central dogma of molecular genetics the flow of genetic information is a one-way road, it always takes the direction from DNA to RNA to protein [16]. In the same year, 1957, Mathew Meselson and Frank Stahl demonstrated the replication mechanism of DNA [17]. In 1958, DNA polymerase became the first enzyme used to make DNA in a test tube. 

Meselson M, Russel K, et al. Comparisons of carcinogenic and mutagenic potency. In Hiatt HH, Watson JD, Winsten JA, eds. Origins of Human Cancer, Book C Human Risk Assessment. Cold Spring Harbor, NY Cold Spring Harbor Laboratory Press, 1977. 

Watson and Crick proposed the hypothesis of semiconservative replication soon after publication of their 1953 paper on the structure of DNA, and the hypothesis was proved by ingeniously designed experiments carried out by Matthew Meselson and Franklin Stahl in... 

The Meselson-Stahl experiment (see Fig. 25-2) proved that DNA undergoes semiconservative replication ini , coli. In the dispersive model of DNA replication, the parent DNA strands are cleaved into pieces of random size, then joined with pieces of newly replicated DNA to yield daughter duplexes. In the Meselson-Stahl experiment, each strand would contain random segments of heavy and light DNA. Explain how the results of Meselson and Stahl s experiment ruled out such a model. 

The role of ATP and S-adenosylmethionine in the reaction remains an intriguing but as yet unresolved question. Recently Yuan and Meselson have reported that in the presence of magnesium ion, ATP and S-adenosylmethionine the R-K endonuclease forms a specific complex with its DNA substrate (55). Complex formation is, however, observed at ATP concentrations (4 X 10-8 M) at which nucleolytic activity is not detectable. This result suggests that ATP may be involved in at least two steps (1) formation of a nonhydrolytic complex at low ATP levels and (2) formation of more stable (or more numerous) complexes and nucleolytic action at higher concentrations of ATP. The S-adenosylmethionine requirement for complex formation is in the same concentration range as observed for restriction. 

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