Review
English
Biju C Mathew 1, Reji Susan Daniel 1, Abdul Nabi 2, Thomas David 3, Paul Augustine 4, John J Bright 5, Ian W Campbell 6
1-Department of Medical Biochemistry, Faculty of Medicine, El Gabal El Gharby University, Gharyan, Libya 2-Faculty of Medicine, El Gabal El Gharby University, Gharyan, Libya 3- Department of Cardiology, Launceston General Hospital Launceston, Australia 4-Division of Surgical Oncology, Regional Cancer Centre, Trivandrum, India 5- Methodist Research Institute, Clarian Health Partners, Indianapolis, United States of America 6-Victoria Hospital, Bute Medical School, University of St Andrews, Scotlan
JMJ 2010, Vol.10, No.2:86-95
Abstract
Telomeres are noncoding sequences of protein-DNA complexes localized at the end of linear chromosomes, which cap and protect the chromosomes and ensure genome stability. Shelterin is a high molecular weight protein complex made up of six proteins TRF1, TRF2, RAP1, TIN2, TPP1, and POT1 which associates with the telomere and protects it from DNA damage response machinery, and also maintain telomere length equilibrium. Because of the ‘end-replication problem’ there is a constant loss of telomeric DNA (50-200 bp), after each normal cell division. Telomerase is a ribonucleoprotein reverse transcriptase that extends the telomeric ends of the chromosomes to counterbalance this natural shortening. Telomerase activity has been detected in more than 80% of most malignant tumors indicating it’s crucial role in the immortalization of cancer cells. Diseases due to attritions in telomeres might be a consequence of primary dysfunction in telomeres or as a secondary effect due to the disease mechanism. Dyskeratosis congenita, aplastic anaemia, acute myeloid leukaemia, paroxysmal nocturnal haemoglobinuria, and pulmonary fibrosis are some diseases linked to telomerase mutations. Recent advances in our understanding of telomere biology indicate that telomerase and telomeres are attractive targets for anticancer therapy. Promising approaches for pharmaceutical intervention include: agents targeting human telomerase RNA component (hTERC), human telomerase reverse transcriptase (hTERT), and telomere, hTERT vaccines, targeting telomerase in tumour-initiating cells, and telomerase-specific virotherapy. High level of telomerase activity has diagnostic and prognostic value in many types of cancer.
Keywords: Telomere, Telomerase, Shelterin, Cancer, Dyskeratosis congenita, Telomerase inhibitors
Link/DOI: http://www.jmj.org.ly/images/stories/summer2010/86.pdf