| dc.description.abstract |
<p>Telomeric sequences are often located internally on the chromosome in addition
to their usual positions at the ends of the chromosome. These internally-located telomeric
sequences have been termed “interstitial telomeric sequences” (ITSs). In humans,
ITSs are non-randomly associated with translocation breakpoints in tumor cells and
with chromosome fragile sites (regions of the chromosome that break in response to
perturbed DNA replication). We previously showed that ITSs in yeast stimulated point
mutations in DNA sequences adjacent to the ITS as well as several types of chromosomal
rearrangements. The major class of these rearrangements was the terminal inversion,
which inverted the chromosome segment between the ITS and the “true” chromosome telomere.
In the current study, we examined the genetic control of these events. We show that
the terminal inversions likely occur by the formation of a double-stranded DNA break
within the ITS, followed by repair of the break utilizing the single-strand annealing
pathway. The point mutations induced by the ITS require the error-prone DNA polymerase
zeta. Unlike the terminal inversions, these events are not initiated by a double-stranded
DNA break, but likely result from error-prone repair of a single-stranded DNA gap
or recruitment of DNA polymerase zeta in the absence of DNA damage.</p>
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