Telomeres: The Molecular Events Driving End-To-End Fusions
نویسنده
چکیده
Recent data indicate that loss of the protective telomeric capping function leads to active degradation of the telomeric G-strand overhang and DNA ligase IV-mediated non-homologous end joining. These molecular events may contribute to genomic instability early in tumorigenesis.
منابع مشابه
End joining at Caenorhabditis elegans telomeres.
Critically shortened telomeres can be subjected to DNA repair events that generate end-to-end chromosome fusions. The resulting dicentric chromosomes can enter breakage-fusion-bridge cycles, thereby impeding elucidation of the structures of the initial fusion events and a mechanistic understanding of their genesis. Current models for the molecular basis of fusion of critically shortened, uncapp...
متن کاملTRF2 Protects Human Telomeres from End-to-End Fusions
The mechanism by which telomeres prevent end-to-end fusion has remained elusive. Here, we show that the human telomeric protein TRF2 plays a key role in the protective activity of telomeres. A dominant negative allele of TRF2 induced end-to-end chromosome fusions detectable in metaphase and anaphase cells. Telomeric DNA persisted at the fusions, demonstrating that TTAGGG repeats per se are not ...
متن کاملDNA Ligase IV-Dependent NHEJ of Deprotected Mammalian Telomeres in G1 and G2
BACKGROUND Telomeres are required to prevent end-to-end chromosome fusions. End-to-end fusions of metaphase chromosomes are observed in mammalian cells with dysfunctional telomeres due to diminished function of telomere-associated proteins and in cells experiencing extensive attrition of telomeric DNA. However, the molecular nature of these fusions and the mechanism by which they occur have not...
متن کاملSpontaneous telomere to telomere fusions occur in unperturbed fission yeast cells
Telomeres protect eukaryotic chromosomes from illegitimate end-to-end fusions. When this function fails, dicentric chromosomes are formed, triggering breakage-fusion-bridge cycles and genome instability. How efficient is this protection mechanism in normal cells is not fully understood. We created a positive selection assay aimed at capturing chromosome-end fusions in Schizosaccharomyces pombe....
متن کاملPARP1 Is a TRF2-associated poly(ADP-ribose)polymerase and protects eroded telomeres.
Poly(ADP-ribose)polymerase 1 (PARP1) is well characterized for its role in base excision repair (BER), where it is activated by and binds to DNA breaks and catalyzes the poly(ADP-ribosyl)ation of several substrates involved in DNA damage repair. Here we demonstrate that PARP1 associates with telomere repeat binding factor 2 (TRF2) and is capable of poly(ADP-ribosyl)ation of TRF2, which affects ...
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عنوان ژورنال:
- Current Biology
دوره 12 شماره
صفحات -
تاریخ انتشار 2002