“Terrific,” “Amazing news,” “Excellent choice,” were some of the terms two UC Davis experts in DNA repair used to describe the award of the 2015 Nobel Prize for Chemistry to three pioneers of the field this morning. The recipients are: Tomas Lindal, Francis Crick Institute, London; Paul Modrich, Howard Hughes Medical Institute and Duke University; and Aziz Sancar of the University of North Carolina Chapel Hill.
“They discovered that DNA in your body, which suffers from millions of DNA damaging events from every day due to normal chemical processes, is repaired efficiently by remarkably complex and disparate sets of repair machineries and mechanisms,” said Stephen Kowalczykowski, distinguished professor of microbiology and molecular genetics in the UC Davis College of Biological Sciences.
Damage to DNA can lead to cancer and birth or developmental defects. Several genes identified as linked to cancer, for example the “breast cancer gene” BRCA2, have turned out to be involved in maintenance or repair of DNA.
“This is a wonderful recognition of the DNA repair field and underlines its importance for general biology and human disease,” said Wolf-Dietrich Heyer, professor and chair of microbiology and molecular genetics, who studies how DNA is repaired during recombination, the process of copying DNA.
Heyer noted connections to work at UC Davis. For example, Professor Sheila David at the Department of Chemistry works on MUTY, a protein that carries out base excision repair, the process discovered by Paul Modrich. David’s laboratory showed how one form of colorectal cancer is caused by a defect in MUTY, Heyer said.
“The approaches taken by all three awardees are the same that Stephen Kowalczykowski and I use to analyze recombinational DNA repair, biochemical reconstitution supported by genetic insights,” Heyer said. Kowalczykowski in particular has pioneered methods to study single molecules at work in DNA repair, allowing insights beyond conventional biochemistry, and has published work in collaboration with Modrich.
The pioneering work by Lindal, Modrich and Sancar brought order and understanding to the field, Kowalczykowski said.
“This understanding allowed the next generation of scientists to probe these biological processes with increasing sophistication. Finally, many, many decades later, we’ve come to learn and understand how defects in these very important repair pathways contribute to cancer development in humans,” Kowalczykowski said.
This work has contributed to human health through new therapies and drugs, a tribute to the value of basic science funded by the public sector and private charities in the U.S. and United Kingdom, he said.
We are only just beginning to appreciate the full impact of DNA repair on the origins and treatment of cancer, Heyer said. Kowalczykowski and Heyer are both members of the UC Davis Comprehensive Cancer Center. The Center’s Molecular Oncology Program is working on both basic mechanisms of DNA repair and translational studies that bring these fundamental insights to the clinic.