Repair at the nuclear periphery

T elomere association with nuclear pores is critical not only for transcriptional silencing but also for effi cient 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 transcrip-tional 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 ef-fi ciency dropped signifi cantly relative to wild-type cells. The ef-fi ciency 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 effi cient 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 chro-matin 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. T he STAT proteins are well-known as signaling proteins and transcription factors. But Ng et al. (page 245) report that Stat3 also functions in the cytoplasm, stabilizing microtubules by directly binding to and inhibiting the activity of a microtubule-destabilizing protein. Stat3 functions in a variety of processes, including proliferation, survival, tumorigenesis, and migration. In each case, except migration, the protein works via transcriptional control of downstream effector proteins. How the protein controls migration is uncertain, though it is clear that cells lacking Stat3 do not migrate effi ciently in vivo or in vitro. Ng et al. found that Stat3 binds to stathmin, a protein that accelerates depolymerization of …