Ben Van Houten, Ph.D., from the University of Pittsburgh, shared his research on new functions for a DNA repair protein known as UV-DDB. He is distinguished by having served at NIEHS as both a lead in-house researcher and a policy manager in the grants program. Van Houten spoke Oct. 5 as part of the Keystone Science Lecture Seminar Series.
Van Houten was introduced by his former scientific staff Janine Santos, Ph.D., from the Genome Integrity and Structural Biology Laboratory (GISBL), and Astrid Haugen, Ph.D., from the Genes, Environment, and Health Branch.
Former colleague Bill Copeland, Ph.D., GISBL chief and lead researcher praised Van Houten. "Ben was a wonderful colleague to have down the hall, with his expertise in NER [nuclear excision repair] and mitochondrial DNA damage,” Copeland said. “He always was and continues to be a great source of advice and encouragement."
Van Houten was surrounded by other colleagues and former trainees as he described his interest in the work of DNA repair enzymes. He shared his fascination with how these proteins assemble onto DNA and how they are able to find different types of damage. Van Houten’s group recently discovered a new role for UV-DDB, a protein involved in repairing ultra-violet light damage to DNA.
Consequences of DNA damage
Cancer is the second most common cause of death in the U.S., exceeded only by heart disease, Van Houten said. He said that one in two men and one in three women will develop cancer in their lifetime, with one in four dying of cancer in the U.S. each year.
Cancer may get its start when damaged DNA is left unrepaired, leading to alterations in the genome that cause problems for the cell.
"The greatest single achievement of nature to date was surely the invention of the molecule of DNA," said Van Houten, quoting from American scientist Lewis Thomas, M.D., in “The Medusa and the Snail.” Van Houten explained that the genius of DNA lies in its capacity to be damaged and then to be repaired.
How bad is DNA damage really?
Cells constantly incur damage to DNA. Unrepaired damage can lead to problems during DNA replication. Van Houten explained that "DNA is the only biomolecule that has dedicated repair pathways." Interestingly, Van Houten worked with Aziz Sancar, M.D., Ph.D., who received the Nobel prize for chemistry in 2015, in recognition of his work on DNA repair.
Two repair pathways that are critical for cells are NER and base excision repair. These repair pathways involve proteins that go through several steps to fix the problem. Briefly, the damage is recognized, verified, cut out, and then filled in with correct bases.
Van Houten presented work on UV-DDB showing that it allows these repair proteins to work better and ensures that the problem is fixed. Furthermore, he described experiments that revealed how repair proteins arrive at the DNA damage site. The presence of UV-DDB enhanced their work to help fix the problem faster.
Van Houten quoted social biologist Edward Wilson, Ph.D. "The greatest challenge today, not just in cell biology and ecology but all of science, is the accurate and complete description of complex systems," Wilson wrote in his book “Consilience.” Van Houten’s next goal is to see, and describe, how these molecules behave in living cells.
(Salahuddin Syed, Ph.D., is an Intramural Research Training Award fellow in the NIEHS DNA Replication Fidelity Group.)