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Description:
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Telomeres are critical for the integrity of eukaryotic genomes . They function to
protect chromosome ends from DNA damage surveillance and inappropriate repair .
Telomeres are maintained by the specialized ribonucleoprotein complex telomerase .
Without telomerase , telomere shortening would ultimately lead to compromised genome
stability and cellular senescence . Therefore , telomerase function is necessary for
extension of the proliferative capacity of the cell .
In this dissertation , we describe the characterization of core components of
telomerase ribonucleoprotein complex in the flowering plant , Arabidopsis thaliana . We
find that dyskerin , one of the core telomerase components in humans is also conserved
in Arabidopsis telomerase . Arabidopsis dyskerin associates with the telomerase RNP in
an RNA -dependent manner and is required for telomere length maintenance in this
organism . We also describe the characterization of another core telomerase component ,
the telomerase RNA subunits (TERs ) . Unexpectedly , we uncovered two distinct TER
subunits that share a region of high identity . The two TERs named TER1G7 and TER5G2 ,
based on their chromosomal positions , display differences in their expression levels and
their association with telomere -related proteins . Both TERs can serve as templates for
telomerase in vitro . Through genetic analyses , we show a templating function for TER1G7 in vivo and a novel role for TER5G2 as a negative regulator of telomerase . Finally , the
presence of TER genes in other plant species was investigated and evidence for
duplication of TER genes in plants closely related to Arabidopsis was obtained . We also
show evidence for a template mutation in Asparagus TER that could lead to variant
repeats in this organism .
In summary , the studies presented in this dissertation reveal that Arabidopsis
telomerase shares both similarities and differences with other telomerase RNPs , making
it an exciting model system for study of telomere biology . |