Attenuated expression of SECIS binding protein 2 causes loss of telomeric reserve without affecting telomerase.
The family of selenoproteins have a broad range of functions, including protection against oxidative damage. Previous studies have shown that elevated levels of oxidative damage can induce accelerated loss of telomeric DNA during proliferation of mammalian cells. The incorporation of selenocysteine (Sec) into proteins in mammalian cells requires the Sec insertion sequence (SECIS) binding protein 2 (SBP2). Thus in the present study we have assessed the effect of knocking down the expression of SBP2 on telomere length. Following knock-down of SBP2 expression in two different human cell lines, the MSTO mesothelioma cell line ( approximately 5Kb average telomere length) and SY5Y neuroblastoma cell line (approximately 4.2Kb average telomere length), we observed a significant reduction (-0.6 to -1.1 Kb; P <or= 0.01) in telomere length as compared to control cells. This reduction in telomere length was independent of affects on telomerase, since both telomerase activity levels and Tert mRNA expression levels were not altered by knock-down of SBP2 expression. Furthermore, telomeres were particularly sensitive to S1 nuclease digestion following SBP2 knock-down, indicating an increased frequency of oxidative damage-induced lesions in the telomeric DNA in these cells. Together, these observations imply that selenoproteins may help protect telomeric reserve in mammalian cells.
Squires
Jeffery E
JE
Cell and Molecular Biology Department, John A Burns School of Medicine, Honolulu, HI 96813, USA.
Davy
Philip
P
Berry
Marla J
MJ
Allsopp
Rich
R
D000375:Aging / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D004249:DNA Damage / Q000235:genetics / Q000502:physiology*; D006801:Humans; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000473:pathology*
D002352:Carrier Proteins; D016601:RNA-Binding Proteins; C121530:SECISBP2 protein, human; D019098:Telomerase