Telomeres are the physical ends of linear chromosomes and form a complex nucleoprotein structure.  The telomere is required both to protect the end of the chromosome from nucleolytic degradation as well as to maintain proper chromosome length.  Loss of telomere function leads to increased genomic instability as well as the induction of cellular senscence.  Interestingly, during the natural aging process telomeres become shorter and genomic instability increases.  One of the main focuses of our lab is to try to better understand the link between telomere regulation and age.

Recently it has been demonstrated that telomeres are transcribed into non-coding TElomeric Repeat containing RNA (TERRA).  Interestingly there is no known function of TERRA, although the levels of TERRA are regulated  as a result of  telomeric alterations, including length and heterochromatic state.

We are using the budding yeast, Saccharomyces cerevisiae, as a model genetic organism to better understand all aspect of TERRA regulation; from biogenesis to function.  The lab uses a variety of  genetic, biochemical, as well as molecular and cell biological assays in order to try to comprehend how TERRA transcription is integrated into telomere regulation and furthermore how this is contolled in terms of aging and may impinge on genomic stability.  Current projects will be focused on determining the function of TERRA in terms of telomere length regulation and the Telomere Position Effect (TPE), as well as trying to find regulators of TERRA transcription and turnover.

Selected publications

Luke B and Lingner J: TERRA: telomere repeat containing RNA. Review article. EMBO J. 2009 Sep 2;28(17):2503-10.

Chang M, Luke B, Kraft C, Li Z, Peter M, Lingner M and Rothstein R: Telomerase is essential to alleviate Pif1-induced replication stress at telomeres. Genetics. 2009 Aug 31. [Epub ahead of print].

Luke B, Panza A,  Redon S, Iglesias N, Li Z, and Lingner J: The Rat1p 5’ to 3’ exonuclease degrades telomeric transcripts and promotes telomere elongation in S. cerevisiae. Mol Cell. 2008 Nov 21;32(4):465-77.

Luke B, Azzalin C, Hug N, Deplazes A, Peter M and Lingner J: Saccharomyces cerevisiae  Ebs1p is a putative ortholog of human SMG7 and promotes nonsense mediated mRNA decay. Nucleic Acids Res. 2007;35(22):7688-97.

Luke B, Versini G, Jaquenoud M, Zaidi IW, Kurz T, Pintard L, Pasero P, Peter M,: The cullin Rtt101p promotes replication fork progression through damaged DNA and natural pause sites. Curr Biol. 2006 Apr 18;16(8):786-92.