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MOLECULE OF THE YEAR
WASHINGTON, D.C.- The envelope please...and the Science magazine 'Molecule of the Year' award goes to...the enzymes that repair damaged DNA. The repair enzymes scan and repair minute errors in DNA by a variety of interesting mechanisms. In addition to protecting the essential elements of genetic information for subsequent generations, the enzymes are the first defense against a number of cancers. Thanks to these enzymes, an average of only three base pair mistakes occur during the replication of the 3 billion base pairs in the human genome. "If the DNA were copied badly, we would have diseases such as cancer at a much higher frequency, and we would not get a faithful copy of our parental inheritance. Our species would not be preserved, and we would not live long. If the DNA were copied perfectly, there would be no room for evolution, and the basis for creation of new species with better environmental adaptation would have vanished long ago. The DNA repair system allows a happy medium," notes Daniel E. Koshland Jr., Editor-in Chief of Science magazine. 1994 saw a series of important research breakthroughs in this area, as scientists reported details of the structure and mechanisms of several of these repair enzymes. The various enzymes collaborate in DNA repair via different mechanisms including mismatch repair, nucleotide excision repair and transcription-coupled nucleotide excision repair. The huge importance of mismatch repair was first reported at the end of 1993, when researchers reported that defects in mismatch repair genes are a primary cause of one type of colorectal cancer. Mismatch repair enzymes specializes in small errors made when DNA is copied. The enzymes check freshly replicated DNA for mispaired bases, cut out the mistakes and fill in the resulting gaps with the correct missing sequences. Other repair enzymes work via nucleotide excision repair. This involves the repair of greater damage to DNA associated with ultraviolet light and toxic chemicals. Defective nucleotide excision repair is associated with a number of disorders including skin cancer, stunted growth, mental retardation, brittle hair or scaly skin. Conversely, DNA damage seen in association with anticancer chemotherapy can be repaired by nucleotide excision repair enzymes. Another type of nucleotide excision repair is linked to transcription. Specialized enzymes repair damage in transcribed genes, which are expressed as proteins, faster than damage in nontranscribed genes. Research conducted in 1994 describing the mechanisms of DNA repair has implications for the diagnoses and treatment of many human diseases. The increased understanding of the repair enzymes is also likely to change the way environmental hazards such as cancer risks are determined. "If we delineate the differences in the metabolism and repair system of the mouse, rat and human, we should be able to explain the discrepancies in tests for carcinogenic potency and perhaps construct a system that accurately mimics the human system," said Dr. Koshland, in an accompanying editorial. This could lead to a much more rational system of risk assessment and could prevent catastrophes such as thalidomide, he notes. For a series of detailed reports on DNA repair enzymes and their significance, see articles by Koshland, Sancar, Hanawalt, Modrich in Science, v.266, 12/23/94.
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Science Updates Index
