title: DNA damage and repair in telomeres: relation to aging.
abstract: We have established a method for the detection of DNA damage and its repair in human telomeres, the natural ends of chromosomes which are necessary for replication and critical for chromosomal stability. We find that ultraviolet light-induced pyrimidine dimers in telomeric DNA are repaired less efficiently than endogenous genes but more efficiently than inactive, noncoding regions. We have also measured telomeric length, telomeric DNA damage, and its repair in relation to the progression of aging. Telomeres are shorter in fibroblasts from an old donor compared to fibroblasts from a young donor, shortest in cells from a patient with the progeroid disorder Werner syndrome, and relatively long in fibroblasts from a patient with Alzheimer disease. Telomeric DNA repair efficiency is lower in cells from an old donor than in cells from a young donor, normal in Alzheimer cells, and slightly lower in Werner cells. It is possible that this decline in telomeric repair with aging is of functional significance to an age-related decline in genomic stability.
authors: Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224.
authors: P A
authors: PA
authors: Kruk
authors: N J
authors: NJ
authors: Rampino
authors: V A
authors: VA
authors: Bohr
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D015139:Blotting, Southern; D002460:Cell Line; D002648:Child; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism* / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007700:Kinetics; D008969:Molecular Sequence Data; D011740:Pyrimidine Dimers; D015183:Restriction Mapping; D016615:Telomere / Q000378:metabolism*; D014466:Ultraviolet Rays; D014898:Werner Syndrome / Q000235:genetics / Q000378:metabolism
chemical_list: D011740:Pyrimidine Dimers; D004247:DNA