Expression of a RecQ Helicase Homolog Affects Progression through Crisis in Fission Yeast Lacking Telomerase

RecQ helicases play roles in telomere maintenance in cancerous human cells using the alternative lengthening of telomeres mechanism and in budding yeast lacking telomerase. Fission yeast lacking the catalytic subunit of telomerase (trt1+) up-regulate the expression of a previously uncharacterized su...

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Bibliographic Details
Published in:The Journal of biological chemistry 2005-02, Vol.280 (7), p.5249-5257
Main Authors: Mandell, Jeffrey G., Goodrich, Karen J., Bähler, Jürg, Cech, Thomas R.
Format: Article
Language:English
Subjects:
Adenosine Triphosphatases - chemistry
Adenosine Triphosphatases - genetics
Adenosine Triphosphatases - metabolism
Amino Acid Sequence
Chromosomes, Fungal - enzymology
Chromosomes, Fungal - genetics
Chromosomes, Fungal - metabolism
Cloning, Molecular
DNA Helicases - chemistry
DNA Helicases - genetics
DNA Helicases - metabolism
Gene Expression Regulation, Fungal
Humans
Molecular Sequence Data
Open Reading Frames - genetics
Phylogeny
Polyribosomes - metabolism
RecQ Helicases
RNA, Fungal - genetics
RNA, Fungal - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Saccharomyces cerevisiae
Schizosaccharomyces - cytology
Schizosaccharomyces - enzymology
Schizosaccharomyces - genetics
Schizosaccharomyces - growth & development
Schizosaccharomyces pombe
Schizosaccharomyces pombe Proteins - chemistry
Schizosaccharomyces pombe Proteins - genetics
Schizosaccharomyces pombe Proteins - metabolism
Sequence Homology, Amino Acid
Telomerase - deficiency
Telomerase - genetics
Telomere - enzymology
Telomere - genetics
Telomere - metabolism
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Summary:RecQ helicases play roles in telomere maintenance in cancerous human cells using the alternative lengthening of telomeres mechanism and in budding yeast lacking telomerase. Fission yeast lacking the catalytic subunit of telomerase (trt1+) up-regulate the expression of a previously uncharacterized sub-telomeric open reading frame as survivors emerge from crisis. Here we show that this open reading frame encodes a protein with homology to RecQ helicases such as the human Bloom's and Werner's syndrome proteins and that copies of the helicase gene are present on multiple chromosome ends. Characterization of the helicase transcript revealed a 7.6-kilobase RNA that was associated with polyribosomes, suggesting it is translated. A 3.6-kilobase domain of the helicase gene predicted to encode the region with catalytic activity was cloned, and both native and mutant forms of this domain were overexpressed in trt1– cells as they progressed through crisis. Overexpression of the native form caused cells to recover from crisis earlier than cells with a vector-only control, whereas overexpression of the mutant form caused delayed recovery from crisis. Taken together, the sequence homology, functional analysis, and site-directed mutagenesis indicate that the protein is likely a second fission yeast RecQ helicase (in addition to Rqh1) that participates in telomere metabolism during crisis. These results strengthen the notion that in multiple organisms RecQ helicases contribute to survival after telomere damage.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M412756200