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1000
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Abstract/Summary
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Telomeres are essential structures that cap the end of chromosomes, which is required for maintenance of chromosomal stability, cell viability and the capacity of cells to proliferate. A complex of specific telomere-binding proteins (TRF1, TRF2, POT1, TIN2, TPP1 and RAP1), also known as the Shelterin complex, is essential for telomere capping by assisting the formation of tertiary telomeric structures.1 Gene mutations in components of the Shelterin complex (hTIN2, hPOT1 and hTPP1) lead to bone marrow failure and cancer formation in human genetic diseases including dyskeratosis congenita (DC), which is caused by Tin2 mutation in 20% of the cases.2, 3 All known TIN2 mutations are heterozygous, autosomal-dominant and patients normally show extremely short telomeres. In addition, mutations in the telomere binding protein POT1 were shown to lead to lymphocytic leukaemia formation.4 Aside from genetic diseases, a variety of studies reported reduced expression of telomere-binding proteins in human cancers compared with non-cancerous tissue suggesting that downregulation of the expression of telomere-binding proteins may also contribute to carcinogenesis in somatic cells and tissues.5, 6 It was shown that Epstein–Barr virus-encoded LMP1 and Epstein–Barr virus-infection itself induce the downregulation of TRF1, TRF2 and POT1 at the transcriptional and translational level resulting in complex chromosomal aberrations, alternative lengthening of telomeres and the induction of Hodgkin's lymphoma.7, 8
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