January 6, 2016
The DNA Damage Response: How Genes Repair Themselves
Evelyn Witkin
Geneticist
The DNA Damage Response: How Genes Repair Themselves
Evelyn Witkin
Geneticist
Claire Jacobus, Introducer, and Evelyn Witkin, Speaker
Minutes of the 14th meeting of the 74th Year
By way of introduction: I was pleased to be asked by John Riganati to do the minutes for Evelyn Witkin’s talk. Why? Because I had met her 68 years ago, in 1947, when she was doing research in the lab at Cold Spring Harbor. I was there, too, as a Princeton junior that summer, doing genetics research on fruit flies.
But I have to tell you that despite my background in genetics, it was very hard for me to comprehend what Dr. Witkin was telling us last week. So don’t feel bad if you had difficulty with her talk. It wasn’t easy for any of us.
And now my 5-minute minutes begin.
At 10:15 a.m. the 14th meeting of the 74th year of the Old Guard was called to order by Owen Leach. One hundred and 10 members were present. Dr. Charles Clark led the invocation. Rhoda Wagman read the minutes of the previous meeting.
Several guests were introduced. Owen Leach introduced Elena Green. Roger Moseley introduced Boris Katz. Rob Kuser introduced David Wetherill. Larry Parsons introduced John Clark. Graydon Vanderbilt introduced Billie Emerich. Green and Wetherill are candidates for membership.
Moments of silence were observed for the recently deceased Old Guard members Seymour Meisel and Rosser Clark.
Claire Jacobus introduced the speaker, Dr. Evelyn Witkin. Dr. Witkin, now 94, has had a long and distinguished career. She attended college at New York University, acquired her Ph.D. from Columbia, and did research in genetics at Cold Spring Harbor and elsewhere; and she was involved in teaching and research at Rutgers University. She has received many awards for her work, most recently the prestigious Lasker Award for Basic Medical Research. Her talk was entitled “The DNA Damage Response: How Genes Repair Themselves.”
Dr. Witkin spoke from her notes, without benefit of PowerPoint illustration. She did provide us with a diagram of the double-helix structure of the gene. Dr. Witkin told us a little of the history of our understanding of genetics. She said that when she began her career, we knew a little about genes but that there was much we did not know. We knew that genes were lined up on chromosomes and that they governed the structure and function of organisms as well as their development. The challenge for genetics was to explain how genes copy themselves to perpetuate their form and their function.
The crucial key to our understanding of how genes work came in 1953, from the elucidation of the double-helix structure of the gene by James Watson and Francis Crick. The two men excitedly bragged that they had found “the secret of life!” Using the technique of X-ray diffraction, Watson and Crick found that genes are constructed in a double-helix (or spiral) formation, composed of multiple units of nucleotides, linked together in two interlocking chains. Each nucleotide is a combination of a nucleobase, a deoxyribose sugar and phosphate. The four nucleobases are adenine, cytosine, guanine and thymine, usually referred to as A, C, G, and T. C always pairs with G, and A pairs only with T. The DNA structure creates a template called messenger RNA which transmits the information to effector regions of the cell, where proteins are synthesized.
Dr. Witkin described her excitement when she learned of this discovery. She turned her genetics research from the fruit fly (Drosophila) to bacteria, which are easier to study. She discovered a strain of bacteria that was resistant to radiation. She noted that in addition to radiation, mutations (or changes in the genome) can also be caused by viruses or by chemical agents. A mutation may be a change in a single place on the nucleotide chain, or a deletion, a duplication or a translocation of genetic material.
Dr. Witkin then provided a complex discussion of various mechanisms for repair of the altered DNA chain. If only one chromatid strand is affected, the healthy strand can be used as a template to guide correction of the damaged strand.
Other mechanisms, such as photoreactivation or methylation may also be involved. In some cases, enzymes activated by light may undergo “scission repair,” or deletion of the damaged segment.
Those repair mechanisms exist in all forms of life, except for organisms in the lightless depths of the sea, or perhaps in dark caves. The repair mechanisms are defective in certain human diseases, for example, xeroderma pigmentosum, in which patients are excessively susceptible to cancers, especially of the skin. UV, or ultraviolet light, she noted, is the cause of most human skin cancers. Defects in DNA repair are also involved in certain kinds of hereditary cancer.
Dr. Witkin’s lengthy discussion allowed for only a couple of questions. But she did comment on the possibilities of gene editing or gene modification, with their possible ethical ramifications.
The meeting was adjourned at 11:30 AM.
Respectfully submitted,
Harvey Rothberg, MD
But I have to tell you that despite my background in genetics, it was very hard for me to comprehend what Dr. Witkin was telling us last week. So don’t feel bad if you had difficulty with her talk. It wasn’t easy for any of us.
And now my 5-minute minutes begin.
At 10:15 a.m. the 14th meeting of the 74th year of the Old Guard was called to order by Owen Leach. One hundred and 10 members were present. Dr. Charles Clark led the invocation. Rhoda Wagman read the minutes of the previous meeting.
Several guests were introduced. Owen Leach introduced Elena Green. Roger Moseley introduced Boris Katz. Rob Kuser introduced David Wetherill. Larry Parsons introduced John Clark. Graydon Vanderbilt introduced Billie Emerich. Green and Wetherill are candidates for membership.
Moments of silence were observed for the recently deceased Old Guard members Seymour Meisel and Rosser Clark.
Claire Jacobus introduced the speaker, Dr. Evelyn Witkin. Dr. Witkin, now 94, has had a long and distinguished career. She attended college at New York University, acquired her Ph.D. from Columbia, and did research in genetics at Cold Spring Harbor and elsewhere; and she was involved in teaching and research at Rutgers University. She has received many awards for her work, most recently the prestigious Lasker Award for Basic Medical Research. Her talk was entitled “The DNA Damage Response: How Genes Repair Themselves.”
Dr. Witkin spoke from her notes, without benefit of PowerPoint illustration. She did provide us with a diagram of the double-helix structure of the gene. Dr. Witkin told us a little of the history of our understanding of genetics. She said that when she began her career, we knew a little about genes but that there was much we did not know. We knew that genes were lined up on chromosomes and that they governed the structure and function of organisms as well as their development. The challenge for genetics was to explain how genes copy themselves to perpetuate their form and their function.
The crucial key to our understanding of how genes work came in 1953, from the elucidation of the double-helix structure of the gene by James Watson and Francis Crick. The two men excitedly bragged that they had found “the secret of life!” Using the technique of X-ray diffraction, Watson and Crick found that genes are constructed in a double-helix (or spiral) formation, composed of multiple units of nucleotides, linked together in two interlocking chains. Each nucleotide is a combination of a nucleobase, a deoxyribose sugar and phosphate. The four nucleobases are adenine, cytosine, guanine and thymine, usually referred to as A, C, G, and T. C always pairs with G, and A pairs only with T. The DNA structure creates a template called messenger RNA which transmits the information to effector regions of the cell, where proteins are synthesized.
Dr. Witkin described her excitement when she learned of this discovery. She turned her genetics research from the fruit fly (Drosophila) to bacteria, which are easier to study. She discovered a strain of bacteria that was resistant to radiation. She noted that in addition to radiation, mutations (or changes in the genome) can also be caused by viruses or by chemical agents. A mutation may be a change in a single place on the nucleotide chain, or a deletion, a duplication or a translocation of genetic material.
Dr. Witkin then provided a complex discussion of various mechanisms for repair of the altered DNA chain. If only one chromatid strand is affected, the healthy strand can be used as a template to guide correction of the damaged strand.
Other mechanisms, such as photoreactivation or methylation may also be involved. In some cases, enzymes activated by light may undergo “scission repair,” or deletion of the damaged segment.
Those repair mechanisms exist in all forms of life, except for organisms in the lightless depths of the sea, or perhaps in dark caves. The repair mechanisms are defective in certain human diseases, for example, xeroderma pigmentosum, in which patients are excessively susceptible to cancers, especially of the skin. UV, or ultraviolet light, she noted, is the cause of most human skin cancers. Defects in DNA repair are also involved in certain kinds of hereditary cancer.
Dr. Witkin’s lengthy discussion allowed for only a couple of questions. But she did comment on the possibilities of gene editing or gene modification, with their possible ethical ramifications.
The meeting was adjourned at 11:30 AM.
Respectfully submitted,
Harvey Rothberg, MD