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Telomerase Subunit Strikes Out on Its Own

Telomerase is a ribonucleoprotein that adds specific DNA repeats to the 3' end of DNA, thereby maintaining the chromosome ends. The enzyme contains a reverse transcriptase and an RNA subunit (hTR) that is used as a template when telomerase elongates telomeres. hTR is ubiquitously expressed and has been found to be essential for telomere maintenance in human disease and mouse models. In this Paper of the Week, Martijn Kedde and colleagues investigate what happens when cellular hTR levels are altered.

hTR enhances the expression of fragile sites.

The researchers found that ectopic expression of hTR inhibits the checkpoint kinase ATR whereas reduction of hTR levels stimulates ATR activity. ATR is a phosphatidylinositol 3-kinaselike protein kinase that coordinates the repair, cell cycle checkpoint, and apoptotic responses to DNA damage. Surprisingly, the hTR-ATR interaction was independent of telomerase activity and telomere length. Furthermore, the researchers found that in response to low UV radiation, which activates ATR, endogenous hTR levels increase independently of the telomerase reverse transcriptase. Thus, Kedde et al. seem to have uncovered a novel, telomerase-independent, function of hTR that restrains ATR activity and participates in cell recovery from UV radiation.

FOOTNOTES

See referenced article, J. Biol. Chem. 2006, 281, 40503-40514

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