| dc.description.abstract | Telomeres protect chromosome ends from being recognized as double-strand
breaks, and respond to incomplete end-replication through telomerase-mediated extension.
POT1 (Protection of Telomere 1) is a highly conserved protein required for capping
chromosome ends and for regulating telomere extension by telomerase. Arabidopsis
thaliana encodes three POT1 paralogues: POT1a, POT1b, and POT1c. POT1a functions to
maintain telomere length homeostasis by promoting telomerase processivity, while POT1b
functions in the DNA damage response. POT1c is derived from a recent duplication of the
POT1a locus, but its function is unknown.
In this dissertation, I examined the function and evolution of POT1c using genetic
and biochemical approach. Unlike pot1a mutants which show defects in telomere
maintenance, plants lacking POT1c exhibit no obvious telomere-related or developmental
phenotypes. Furthermore, the POT1c gene is not expressed under standard growth
conditions. Transposable elements (TE) are embedded in the POT1c promoter region; yet,
active silencing is not observed. Although POT1a and the dS17 gene, which was created in
the same duplication event that gave rise to POT1c, are highly conserved among A.
thaliana accessions, POT1c is not. Comparison of POT1a and POT1c loci from species
closely related to A. thaliana and A. lyrata indicates that POT1c initially had a functional
promoter that was subsequently disrupted by TE insertion. Together, these studies provide
new insights into the fate of newly duplicated genes, and the importance of proper
regulation of telomere proteins.
In addition to the study of the POT1c locus, I have analyzed a newly identified
gene (NOP2A) that is implicated in the control of telomere length set point. NOP2A is a
conserved rRNA methyltransferase protein that positively correlates with cell proliferation.
Telomere length is variable across eukaryotes, but each species establishes a specific set
point that allows full protection for chromosome ends. My research shows that mutation in
NOP2A locus leads to shorter, but stable telomere length in the Col-0 accession of A.
thaliana. These findings provide strong evidence that additional genes that regulate
telomeres remain to be discovered. | en |
