New ways not to make ends meet: telomerase, DNA damage proteins and heterochromatin.
Oncogene
; 21(4): 553-63, 2002 Jan 21.
Article
em En
| MEDLINE
| ID: mdl-11850780
ABSTRACT
Telomeres are stabilized, and telomeric DNA is replenished, by the action of the ribonucleoprotein reverse transcriptase telomerase. Telomere capping functions include the ability of telomeres to protect chromosome ends from cellular DNA-damage responses such as cell cycle arrest or apoptosis. This property of telomeres is especially important for cancer cells, which continue proliferating despite chromosome aberrations. Telomere capping is influenced by multiple, mutually reinforcing factors including telomere length, although telomere length is only one of several determinants of telomere functionality. For example, many cancer cells express high levels of telomerase yet maintain relatively short telomeres. We consider three aspects of telomere capping that have emerged relatively recently (1) a new role for telomerase in telomere capping independent of its function in telomere elongation. Support for this novel function comes from experiments showing an increase in replicative potential with the reactivation of telomerase, without net telomere lengthening; (2) the role at telomeres of DNA damage proteins. We propose a model in which two factors specifically target telomeres for the action of telomerase, as opposed to recombination or non-homologous end-joining binding by telomeric proteins that limits DNA damage responses at telomeres, and the affinity of the telomerase RNP for telomeric proteins and DNA; and (3) we discuss a potential protective role of amplified subtelomeric DNAs, which may aid capping of telomeres maintained by non-telomerase based mechanisms through the formation of heterochromatin.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Proteínas Nucleares
/
Telômero
/
Telomerase
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article