Telomere sister chromatid exchange and the process of aging.
Telomeres are a hotspot for sister chromatid exchange (T-SCE). Any biological consequence of this form of instability remained obscure until quantitative modeling revealed a link between elevated T-SCE rates and accelerated cellular replicative senescence. This work strongly suggests that progressive telomere erosion is not the only determinant of replicative capacity; instead, T-SCE need to be considered as an independent factor controlling colony growth and senescence. Additionally high T-SCE rates have been observed in cells with deficiencies in WRN and BLM, the genes that are defective in Werner's and Bloom's syndromes, implying a connection to premature aging. In this Research Perspective we will explore some of the implications this recent work has for human health.
National Science Foundation, Arlington, VA 22230, USA.
Krastan B
KB
Blagoev
Edwin H
EH
Goodwin
Susan M
SM
Bailey
D000375:Aging / Q000235:genetics; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001816:Bloom Syndrome / Q000235:genetics; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000502:physiology*; D003198:Computer Simulation; D005090:Exodeoxyribonucleases / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics; D053484:RecQ Helicases / Q000235:genetics; D012854:Sister Chromatid Exchange / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D015595:Skin Aging / Q000235:genetics / Q000528:radiation effects; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D014898:Werner Syndrome / Q000235:genetics; D000071657:Werner Syndrome Helicase
D000975:Antioxidants; D005090:Exodeoxyribonucleases; C097151:Bloom syndrome protein; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase