Transcription of telomeric DNA leads to high levels of homologous recombination and t-loops.
Kar A, Willcox S, Griffith JD
Nucleic Acids Res (2016) in press
Category: telomere ¤ Added: Sep 16, 2016 ¤ Rating: ◊◊
The formation of DNA loops at chromosome ends (t-loops) and the transcription of telomeres produc- ing G-rich RNA (TERRA) represent two central fea- tures of telomeres. To explore a possible link be- tween them we employed artificial human telomeres containing long arrays of TTAGGG repeats flanked by the T7 or T3 promoters. Transcription of these DNAs generates a high frequency of t-loops within in- dividual molecules and homologous recombination events between different DNAs at their telomeric se- quences. T-loop formation does not require a single strand overhang, arguing that both terminal strands insert into the preceding duplex. The loops are very stable and some RNase H resistant TERRA remains at the t-loop, likely adding to their stability. Tran- scription of DNAs containing TTAGTG or TGAGTG re- peats showed greatly reduced loop formation. While in the cell multiple pathways may lead to t-loop for- mation, the pathway revealed here does not depend on the shelterins but rather on the unique character of telomeric DNA when it is opened for transcription. Hence, telomeric sequences may have evolved to fa- cilitate their ability to loop back on themselves.