Abstract:
:Some human cancers maintain their telomeres using the alternative lengthening of telomeres (ALT) mechanism; a process thought to involve recombination. Different types of recombinational telomere elongation pathways have been identified in yeasts. In senescing yeast telomerase deletion (ter1-Delta) mutants with very short telomeres, it has been hypothesized that copying a tiny telomeric circle (t-circle) by a rolling circle mechanism is the key event in telomere elongation. In other cases more closely resembling ALT cells, such as the stn1-M1 mutant of Kluyveromyces lactis, the telomeres appear to be continuously unstable and routinely reach very large sizes. By employing two-dimensional gel electrophoresis and electron microscopy, we show that stn1-M1 cells contain abundant double stranded t-circles ranging from approximately 100 to 30,000 bp in size. We also observed small single-stranded t-circles, specifically composed of the G-rich telomeric strand and tailed circles resembling rolling circle replication intermediates. The t-circles most likely arose from recombination events that also resulted in telomere truncations. The findings strengthen the possibility that t-circles contribute to telomere maintenance in stn1-M1 and ALT cells.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Basenko EY,Cesare AJ,Iyer S,Griffith JD,McEachern MJdoi
10.1093/nar/gkp814subject
Has Abstractpub_date
2010-01-01 00:00:00pages
182-9issue
1eissn
0305-1048issn
1362-4962pii
gkp814journal_volume
38pub_type
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