Telomere Dysfunction Increases Mutation Rate and Genomic Instability

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dc.contributor.author Greider, Carol W.
dc.contributor.author Feldser, David M.
dc.contributor.author Hackett, Jennifer A.
dc.date.accessioned 2009-11-28T16:10:40Z
dc.date.available 2009-11-28T16:10:40Z
dc.date.issued 2001-08-10
dc.identifier.citation Reprinted from Cell 106, Hackett, Jennifer A., et al, "Telomere Dysfunction Increases Mutation Rate and Genomic Instability", pg. 275-286, copyright 2001 with permission from Elsevier. Original version available at http://www.cell.com en
dc.identifier.uri http://jhir.library.jhu.edu/handle/1774.2/33667
dc.description.abstract The increased tumor incidence in telomerase null mice suggests that telomere dysfunction induces genetic instability. To test this directly, we examined mutation rate in the absence of telomerase in S. cerevisiae. The mutation rate in the CAN1 gene increased 10- to 100- fold in est1􏰋 strains as telomeres became dysfunc- tional. This increased mutation rate resulted from an increased frequency of terminal deletions. Chromo- some fusions were recovered from est1􏰋 strains, sug- gesting that the terminal deletions may occur by a breakage-fusion-bridge type mechanism. At one lo- cus, chromosomes with terminal deletions gained a new telomere through a Rad52p-dependent, Rad51p- independent process consistent with break-induced replication. At a second locus, more complicated re- arrangements involving multiple chromosomes were seen. These data suggest that telomerase can inhibit chromosomal instability. en
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dc.description.provenance Made available in DSpace on 2009-11-28T16:10:40Z (GMT). No. of bitstreams: 1 Cell2001-2.pdf: 920301 bytes, checksum: 887009fc0c6a3e271d07bfb88c88b778 (MD5) Previous issue date: 2001-08-10 en
dc.language.iso en_US en
dc.publisher Cell Press en
dc.subject Telomere/genetics en
dc.subject Saccharomyces cerevisiae/genetics en
dc.subject Mutagenesis/genetics en
dc.subject Chromosome Aberrations/genetics en
dc.subject Amino Acid Transport Systems en
dc.title Telomere Dysfunction Increases Mutation Rate and Genomic Instability en
dc.type Article en

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