Telomerase core components protect Candida telomeres from aberrant overhang accumulation

doi:10.1073/pnas.0700327104

Telomerase core components protect Candida telomeres from aberrant overhang accumulation

*Department of Microbiology and Immunology, W. R. Hearst Microbiology Research Center, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021; and
^†Departments of Biochemistry and Biophysics and of Microbiology and Immunology, University of California, San Francisco, CA 94143

Edited by Mary-Lou Pardue, Massachusetts Institute of Technology, Cambridge, MA, and approved May 24, 2007 (received for review January 12, 2007)

Abstract

Telomerase is a cellular reverse transcriptase that extends one strand (the G-strand) of the telomere terminal repeats. Aside from this role in telomere length maintenance, telomerase has been proposed to serve a protective function at chromosome ends, although this is not well understood mechanistically. Earlier analysis suggests that, in the pathogenic yeast Candida albicans, the catalytic reverse transcriptase subunit of telomerase (TERT/EST2) can protect telomeres against nucleolytic degradation. In this report we demonstrate that the RNA component (TER1) has a similar function; in addition to complete loss of telomerase activity and progressive telomere attrition, the ter1-ΔΔ strains manifested a dramatic increase in the amount of G-strand overhangs, consistent with aberrant degradation of the complementary C-strand. We also demonstrate that a catalytically incompetent EST2 protein can suppress such overhang accumulation in the est2-ΔΔ mutant to the same extent as the wild-type protein. Altogether, our data support the notion that the Candida telomerase core components mediate a protective function through a mechanism that is independent of its catalytic activity.

Footnotes

^¶To whom correspondence should be addressed. E-mail: nflue{at}med.cornell.edu
Author contributions: M.H., M.J.M., A.T.D., Y.T., E.H.B., and N.F.L. designed research; M.H., M.J.M., A.T.D., Y.T., E.O., E.H.B., and N.F.L. performed research; M.H., M.J.M., A.T.D., Y.T., E.H.B., and N.F.L. analyzed data; and N.F.L. wrote the paper.
↵ ^‡Present address: Department of Genetics, University of Georgia, Fred C. Davidson Life Sciences Complex, Athens, GA 30602.
↵ ^§Present address: Department of Genetics, The Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0700327104/DC1.
Abbreviations:

TERT,

telomerase reverse transcriptase;

TER1,

telomerase RNA 1.