NDLI: The nature of telomere fusion and a definition of the critical telomere length in human cells

Content Provider	PubMed Central
Author	Capper, Rebecca Britt-compton, Bethan Maira, Tankimanova Rowson, Jan Letsolo, Boitelo Man, Stephen Haughton, Michele Baird, Duncan M.
Copyright Year	2007
Abstract	The loss of telomere function can result in telomeric fusion events that lead to the types of genomic rearrangements, such as nonreciprocal translocations, that typify early-stage carcinogenesis. By using single-molecule approaches to characterize fusion events, we provide a functional definition of fusogenic telomeres in human cells. We show that approximately half of the fusion events contained no canonical telomere repeats at the fusion point; of those that did, the longest was 12.8 repeats. Furthermore, in addition to end-replication losses, human telomeres are subjected to large-scale deletion events that occur in the presence or absence of telomerase. Here we show that these telomeres are fusogenic, and thus despite the majority of telomeres being maintained at a stable length in normal human cells, a subset of stochastically shortened telomeres can potentially cause chromosomal instability. Telomere fusion was accompanied by the deletion of one or both telomeres extending several kilobases into the telomere-adjacent DNA, and microhomology was observed at the fusion points. This contrasted with telomere fusion that was observed following the experimental disruption of TRF2. The distinct error-prone mutational profile of fusion between critically shortened telomeres in human cells was reminiscent of Ku-independent microhomology-mediated end-joining.
Related Links	http://dx.doi.org/10.1101/gad.439107
Ending Page	2508
Page Count	14
Starting Page	2495
File Format	PDF
ISSN	08909369
e-ISSN	15495477
Journal	Genes & Development
Issue Number	19
Volume Number	21
Language	English
Publisher	Cold Spring Harbor Laboratory Press
Publisher Date	2007-10-01
Access Restriction	Open
Rights Holder	Cold Spring Harbor Laboratory Press
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Developmental Biology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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The nature of telomere fusion and a definition of the critical telomere length in human cells.

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The nature of telomere fusion and a definition of the critical telomere length in human cells.

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