title: Telomerase deficiency and cancer susceptibility syndromes.
abstract: Telomeres from most eukaryotes are composed of repeats of guanine-rich sequences whose main function is to preserve the end of the chromosomes. Telomeres are synthesised by a reverse transcriptase enzyme, telomerase (TERT), which forms part of a ribonucleoprotein complex containing also a RNA template molecule (TERC) and dyskerin. Exhaustion of telomeres during cell divisions triggers a DNA damage response that induces a senescence phenotype. The DNA damage machinery plays an essential role in maintaining the integrity of the genome and also detecting telomere shortening. However in some syndromes that involved mutations either in the telomerase complex genes or those involved in maintaining DNA secondary structure, such as the recQ helicase WRN, a higher frequency in the development of different types of malignancies is observed. We here describe the biology of some of these diseases, together with the molecular modifications in the telomerase complex genes and the impact of these alterations on the development of particular types of cancer.
authors.affiliation: Instituto de Investigaciones Biomédicas CSIC/UAM, Translational Oncology Unit, Madrid, Spain. rperona@iib.uam.es
authors.forename: Rosario
authors.initials: R
authors.lastname: Perona
authors.forename: Rosario
authors.initials: R
authors.lastname: Machado-Pinilla
authors.forename: Cristina
authors.initials: C
authors.lastname: Manguan
authors.forename: Jaime
authors.initials: J
authors.lastname: Carrillo
mesh_terms: D000818:Animals; D004249:DNA Damage; D019871:Dyskeratosis Congenita / Q000235:genetics; D005090:Exodeoxyribonucleases / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D023281:Genomics; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D053484:RecQ Helicases / Q000378:metabolism; D019098:Telomerase / Q000172:deficiency* / Q000378:metabolism; D016615:Telomere / Q000648:ultrastructure; D014898:Werner Syndrome / Q000235:genetics; D000071657:Werner Syndrome Helicase
chemical_list: C422952:telomerase RNA; D012313:RNA; D019098:Telomerase; D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase