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Nucleic Acids Research 2004 32(12):3743-3751; doi:10.1093/nar/gkh691
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Published online 16 July 2004

Nucleic Acids Research, Vol. 32 No. 12 © Oxford University Press 2004; all rights reserved

Frequent recombination in telomeric DNA may extend the proliferative life of telomerase-negative cells

Susan M. Bailey1,4, Mark A. Brenneman2,3 and Edwin H. Goodwin4,*

1 Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA, 2 Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA, 3 Department of Genetics, Rutgers University, Piscataway, NJ 08854, USA and 4 Bioscience Division, Los Alamos National Laboratory, MS M888, Los Alamos, NM 87545, USA

* To whom correspondence should be addressed. Tel: +1 505 665 2853; Fax: +1 505 665 3024; Email: egoodwin{at}lanl.gov

Received April 30, 2004; Revised and Accepted June 18, 2004

For cells on the path to carcinogenesis, the key to unlimited growth potential lies in overcoming the steady loss of telomeric sequence commonly referred to as the ‘end-replication problem’ that occurs with each cell division. Most human tumors have reactivated telomerase, a specialized reverse transcriptase that directs RNA-templated addition of telomeric repeats on to chromosomal termini. However, ~10% of tumors maintain their telomeres through a recombination-based mechanism, termed alternative lengthening of telomeres or ALT. Here we demonstrate that telomeric DNA undergoes a high rate of a particular type of recombination visualized cytogenetically as sister chromatid exchange (SCE), and that this rate is dependent on genotype. A novel model of ALT is presented in which it is argued that telomeric exchanges, if they are unequal and occur at a sufficiently high frequency, will allow cells to proliferate indefinitely without polymerase-mediated extension of telomeric sequence.


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