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 preferentialy repaired. This appears to be the case as genes we have examined in that component of the cell structure are efficiently repaired. We have also sought to investigate 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

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000724-11
Application #
6815305
Study Section
(LMG)
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2003
Total Cost
Indirect Cost
Name
Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Bohr, V A (2002) DNA damage and its processing. relation to human disease. J Inherit Metab Dis 25:215-22
Thorslund, Tina; Sunesen, Morten; Bohr, Vilhelm A et al. (2002) Repair of 8-oxoG is slower in endogenous nuclear genes than in mitochondrial DNA and is without strand bias. DNA Repair (Amst) 1:261-73
Rosner, K; Winter, D B; Tarone, R E et al. (2001) Third complementarity-determining region of mutated VH immunoglobulin genes contains shorter V, D, J, P, and N components than non-mutated genes. Immunology 103:179-87
Rosner, K; Winter, D B; Skovgaard, G L et al. (2001) Analysis of microsatellite instability and hypermutation of immunoglobulin variable genes in Werner syndrome. Mech Ageing Dev 122:1121-33