Published 16 January 2006. doi:10.1083/jcb1722iti1
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 172, Number 2, 164-164
Repair at the nuclear periphery
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Cells lacking some nucleoporins die on FOA because they derepress a telomeric URA3 gene.
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Telomere association with nuclear pores is critical not only for transcriptional silencing but also for efficient repair of double-stranded breaks in the subtelomeric region of budding yeast chromosomes, according to Therizols et al. (page 189).
As in many organisms, yeast telomeres localize to the nuclear periphery. To determine whether nuclear pore proteins are involved in telomere tethering, Therizols et al. looked for telomere localization in cells lacking functional Nup84 complexes, which are essential components of the pore. They found that the telomeres no longer associated with the nuclear periphery in these mutants.
As might be expected from previous work on transcriptional silencing, transgenes located in the subtelomeric region were no longer silent in Nup84 complex mutants, indicating that localization of the telomere to the nuclear periphery was functionally important.
Surprisingly, when double-stranded breaks were introduced into subtelomeric sites in the mutants, DNA repair efficiency dropped significantly relative to wild-type cells. The efficiency of break repair in central regions of chromosomes did not differ between wild-type and mutant cells.
The DNA silencing and repair phenotypes were separated in cells mutant for Esc1p, a protein located at the nuclear periphery but which is not directly involved in the pore. In this case, telomere localization and DNA repair were disrupted, but silencing remained intact.
The researchers conclude that anchoring telomeres to the nuclear pore is important for efficient DNA double-stranded break repair in the subtelomeric regions, though it is not yet clear why this is true. Because silencing remained intact in the Esc1p mutants but repair was disrupted, it appears that chromatin structure itself is not the problem. One possibility is that clusters of repair proteins may be concentrated near groups of tethered telomeres, thereby facilitating rapid repairs.
Rabiya S. Tuma
rabiya@nasw.org
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Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region
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