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Published online: 3 February 2010 | doi:10.1038/nchina.2010.14

Structural biology: Make up a foursome

Felix Cheung

Introduction

© (2010) Nature Structural & Molecular Biology

Telomeres are the physical ends of chromosomes, composed of guanine-rich single-stranded DNA (G-rich ssDNA) and binding proteins. Cells must maintain their telomeres in good condition or they cannot undergo normal cell division. Most cells use a specialized enzyme called telomerase to repair and lengthen their telomeres, but the details of the underlying mechanisms remain unknown. Jinqiu Zhou and co-workers at the Chinese Academy of Sciences in Shanghai¹ have now characterized the yeast telomerase subunit Est1p and found that it has the ability to promote the conversion of G-rich ssDNA into the highly complex structure required for telomere elongation.

The telomerase in the budding yeast Saccharomyces cerevisiae contains four subunits: Est1p, Est2p, Est3p and Tlc1. In particular, Est2p and Tlc1 are known to form a complex that is able to catalyze telomere elongation, whereas Est1p is known to have an essential role in telomere replication. Recent observations, however, suggest that Est1p has an as-yet-unknown role in telomere elongation.

The researchers therefore purified Est1p from yeast and examined its biochemical activity. They discovered that Est1p was able to support cell growth with short but stable telomeres. They also found that the overexpression of Est1p led to longer telomeres in yeast, but the overexpression or co-overexpression of Est2p, Est3p and Tlc1 caused little change in telomere length.

Further studies revealed that Est1p promotes G-rich ssDNA to form a four-stranded structure called G-quadruplex (pictured), which activates the Est2p–Tlc1 complex. The researchers found that cells carrying Est1p mutants had gradual telomere shortening and cellular senescence.

Taken together, the findings demonstrate that Est1p has the guanine quadruplex-promoting activity that is required for telomere elongation.

The authors of this work are from:
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Reference

1. Zhang, M. L. et al. Yeast telomerase subunit Est1p has guanine quadruplex–promoting activity that is required for telomere elongation. Nature Struct. Mol. Biol. doi:10.1038/nsmb.1760 (2010). | Article