@article{aefc0e93c7d24c2582a26eea3a8504a0,
title = "Balancing instability: Dual roles for telomerase and telomere dysfunction in tumorigenesis",
abstract = "Telomere shortening and telomerase activation both occur in human tumors. Telomere shortening has been proposed to have two conflicting roles in tumorigenesis: tumor suppression and initiation of chromosomal instability. Similarly, while telomerase activation is suggested to be necessary for tumor growth, telomerase may help to stabilize genomic instability. Here we review what is known about these conflicting roles and propose a framework to understand the role of telomerase in cancer progression.",
keywords = "Chromosomal instability, Telomerase, Telomeres",
author = "Hackett, {Jennifer A.} and Greider, {Carol W.}",
note = "Funding Information: We thank David Feldser, Mike Hemann, Doug Mason, Ling Qi, and Margaret Strong for critical reading of the manuscript. JA Hackett was supported by the Predoctoral Training Program in Human Genetics and Molecular Biology and a National Science Foundation Graduate Research Fellowship. This work was supported by NIH grant GM43080 to CW Greider. Funding Information: In addition to the possible role of telomerase in preventing the initiation of chromosomal instability by maintaining telomere function, telomerase might also suppress mutagenic chromosome fusions that facilitate breakage-fusion-bridge (BFB) cycles by allowing telomere addition to repair broken ends. The role of telomerase in halting BFB cycles is supported by the work of Barbara McClintock. When a broken chromosome is transmitted to the endosperm in maize, BFB continues during the development of the endosperm. However, if a broken chromosome is transferred to the zygote, the broken end is healed and no BFB occurs (). The presence of BFB in the endosperm, but not in the embryo may result from the presence of significant telomerase activity in the embryo, but not in the endosperm () which allows telomerase to add a new telomere to broken ends in the embryo. Telomerase-mediated de novo telomere addition has been demonstrated as a mechanism for healing broken chromosomes in yeast (). In support of the role of telomere addition in limiting BFB, yeast that undergo gross chromosomal rearrangements are more likely to contain chromosome fusions and rearrangements involving multiple chromosomes in the absence of telomerase than when telomerase is present (; ). ",
year = "2002",
month = jan,
day = "21",
doi = "10.1038/sj/onc/1205061",
language = "English (US)",
volume = "21",
pages = "619--626",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "4 REV. ISS. 1",
}