Telomere length maintenance--an ALTernative mechanism.
The Alternative Lengthening of Telomeres (ALT) mechanism is utilised by approximately 10% of human tumours and a higher proportion of some types of sarcomas. ALT+ cell lines and tumours show heterogeneous telomere length, extra-chromosomal circular and linear telomeric DNA, ALT associated promyelocytic bodies (APBs), a high frequency of post-replication exchanges in telomeres (designated as telomere-sister chromatid exchanges, T-SCE) and high instability at a GC-rich minisatellite, MS32 (D1S8). It is clear that there is a link between the minisatellite instability and the mechanism that underpins ALT, however currently the nature of this relationship is uncertain. Single molecule analysis of telomeric DNA from ALT+ cell lines and tumours has revealed complex telomere mutations that have not been seen in cell lines or tumours that express telomerase. These complex telomere mutations cannot be explained by T-SCE but must arise by another inter-molecular process. The break-induced replication (BIR) model that may explain the observed high frequency of T-SCE and the presence of complex telomere mutations is reviewed.
Royle
N J
NJ
Department of Genetics, University of Leicester, Leicester, UK. njr@le.ac.uk
Foxon
J
J
Jeyapalan
J N
JN
Mendez-Bermudez
A
A
Novo
C L
CL
Williams
J
J
Cotton
V E
VE
D017398:Alternative Splicing; D002460:Cell Line; D004247:DNA / Q000235:genetics; D004271:DNA, Fungal / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D042822:Genomic Instability; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D012509:Sarcoma / Q000201:enzymology / Q000235:genetics; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000648:ultrastructure
D004271:DNA, Fungal; D004273:DNA, Neoplasm; D004247:DNA; D019098:Telomerase