Abstract:
:Considerable evidence now supports the idea that the moderate telomere lengthening produced by recombinational telomere elongation (RTE) in a Kluyveromyces lactis telomerase deletion mutant occurs through a roll-and-spread mechanism. However, it is unclear whether this mechanism can account for other forms of RTE that produce much longer telomeres such as are seen in human alternative lengthening of telomere (ALT) cells or in the telomerase-resistant type IIR "runaway" RTE such as occurs in the K. lactis stn1-M1 mutant. In this study we have used mutationally tagged telomeres to examine the mechanism of RTE in an stn1-M1 mutant both with and without telomerase. Our results suggest that the establishment stage of the mutant state in newly generated stn1-M1 ter1-Δ mutants surprisingly involves a first stage of sudden telomere shortening. Our data also show that, as predicted by the roll-and-spread mechanism, all lengthened telomeres in a newly established mutant cell commonly emerge from a single telomere source. However, in sharp contrast to the RTE of telomerase deletion survivors, we show that the RTE of stn1-M1 ter1-Δ cells produces telomeres whose sequences undergo continuous intense scrambling via recombination. While telomerase was not necessary for the long telomeres in stn1-M1 cells, its presence during their establishment was seen to interfere with the amplification of repeats via recombination, a result consistent with telomerase retaining its ability to add repeats during active RTE. Finally, we observed that the presence of active mismatch repair or telomerase had important influences on telomeric amplification and/or instability.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Xu J,McEachern MJdoi
10.1371/journal.pgen.1003017subject
Has Abstractpub_date
2012-01-01 00:00:00pages
e1003017issue
11eissn
1553-7390issn
1553-7404pii
PGENETICS-D-12-00668journal_volume
8pub_type
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