TY - JOUR
T1 - Telomerase core components protect Candida telomeres from aberrant overhang accumulation
AU - Hsu, Min
AU - McEachern, Michael J.
AU - Dandjinou, Alain T.
AU - Tzfati, Yehuda
AU - Orr, Erica
AU - Blackburn, Elizabeth H.
AU - Lue, Neal F.
PY - 2007/7/10
Y1 - 2007/7/10
N2 - 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.
AB - 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.
KW - G-strand
KW - Telomerase RNA
KW - Telomerase reverse transcriptase
UR - http://www.scopus.com/inward/record.url?scp=34547422265&partnerID=8YFLogxK
U2 - 10.1073/pnas.0700327104
DO - 10.1073/pnas.0700327104
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C2 - 17609387
AN - SCOPUS:34547422265
SN - 0027-8424
VL - 104
SP - 11682
EP - 11687
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 28
ER -