Uracil Positioning Affects Efficiency of Base Excision Repair Enzymes

Michael Smerdon, Ph.D., Washington State University and
Samuel Wilson, NIEHS
R01ES04106

Background: DNA damage can occur from a wide variety of environmental agents including UV and other sources of ionizing radiation and cancer-causing chemicals. As a major defense against environmental damage to cells, DNA repair systems are present in organisms as diverse as bacteria, yeast, fruit flies, fish, amphibians, rodents and humans. DNA repair is involved in processes that minimize cell killing, mutations, DNA copying errors, and genomic instability. Abnormalities in repair processes have been implicated in cancer and aging.

Advance: Researchers at the University of Washington and the National Institute of Environmental Health Sciences report here that DNA repair enzymes do a much better job of repairing damaged DNA depending on whether the orientation of repair enzymes is toward or away from nucleosomes. Nucleosomes are complexes of chromatin material and chromosomal protein structures known as histones. Histones act as spools around which DNA winds, thus facilitating its compaction so that the large genomes of advanced animals will fit into every cell nucleus.

Implication: This novel finding represents a new model for studying DNA repair and opens new insights into the efficiency of repair processes. It also has implications in possible therapeutic treatments aimed at improving repair mechanisms to prevent and treat serious diseases associated with DNA repair abnormalities such as cancer and Alzheimer's.

Citation: Beard BC, Wilson SH, Smerdon MJ. Suppressed catalytic activity of base excision repair enzymes on rotationally positioned uracil in nucleosomes. Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7465-70. Epub 2003 Jun 10.