IMBICE   05372
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA CELULAR
Unidad Ejecutora - UE
capítulos de libros
Título:
An overview of the biological functions of telomeres
Autor/es:
ALEJANDRO D. BOLZAN
Libro:
Telomeres: Biological Functions, Sequencing and Aging
Editorial:
Nova Science Publishers
Referencias:
Año: 2012; p. 79 - 97
Resumen:
Telomeres are specialized nucleoproteic complexes localized at the physical ends of linear eukaryotic chromosomes that maintain their stability and integrity. In mammalian cells, telomeres consist of tandem arrays of the repetitive sequence (TTAGGG)n, oriented 5' to 3' towards the end of the chromosomes and associated proteins, and a large non-coding RNA (named TERRA) which forms an integral component of telomeric heterochromatin. Telomeres provide a protective "cap" for chromosomal DNA against illegitimate recombination, exonucleolytic attack and degradation, and oxidative damage. The main role of telomeres is to preserve the integrity of the chromosomes, protecting them from degradation, recombination or fusion, by preventing the ends of linear chromosomes from being recognized as DNA double-strand breaks (DSB) by the DNA repair machinery, i.e., they distinguish natural DNA ends from DNA ends resulting from breakage events. Besides the abovementioned function, telomeres regulate the replicative life span of somatic cells, contribute to maintenance of chromosome topology in the cell nucleus, play a fundamental role in the proper alignment of chromosomes for recombination during the first meiotic prophase, assure accurate chromosome segregation during mitosis, and silence genes flanking the telomere repeat sequence, a phenomenon called the "telomere position effect". The maintenance of telomere function is crucial for genomic stability and cell viability. Cells respond to dysfunctional telomeres by undergoing senescence, cell death, or genomic instability. Moreover, telomere dysfunction has been identified as a primary mechanism involved in the chromosomal instability observed in cancer cells. Cellular response to dysfunctional telomeres is governed by proteins that also control the DNA damage response. In addition, several aspects of telomere form and function are modulated by the enzymes helicases. The present review offers an overview of the many biological functions of telomeres in mammalian cells.