Gene Specific DNA Repair

Bohr, Vilhelm

Abstract

of work: DNA repair can be studied at the level of the whole genome, in specific regions, in specific genes, or in transcribed or nontranscribed DNA. We have had an ongoing interest in the repair that takes place in genes and how it relates to gene function and cellular survival. We have examined the repair of several essential genes and various structural genes. We also examined whether genes associated with the nuclear matrix were preferentially repaired. We are investigating whether somatic hypermutation is assocaited with DNA repair changes in the immunglobulin genes involved. This has becme highly relevant with the recent discovery that somatic hypermutation is associated with the base excision DNA repair pathway via the AID protein. The nematode has been a very useful model system for the study of aging. There are important mutants of many kinds including some with increased life span. These mutants with increased life span also are hyperresistant to various kinds of cellular damage, including UV irradiation and oxidative stress. By gene specific analysis of various gene regions in the nematode we seek to clarify whether the increased life span is associated with an increase in gene specific DNA repair. It is difficult to establish assays for gene repair in nematodes, but we have recently had progress with these measurements.