When centromeres fill in for telomeres

نویسنده

  • Ben Short
چکیده

Klebba and Galletta et al. reveal that the scaffold protein Asterless (Asl) regulates centriole duplication by controlling turnover of the kinase Plk4. Cells must duplicate their centri-oles once, and only once, per cell cycle. In interphase, the master regulator of centriole duplication, Plk4, triggers its own destruction by homodimerizing and phosphorylating itself. In mitosis, however, the phosphatase PP2A reverses this phosphorylation and stabilizes Plk4, allowing the kinase to accumulate on the surface of the mother centriole and license the assembly of a daughter centriole in the following S phase. Plk4 localizes to centrioles by binding to the N terminus of Asl. Surprisingly, given that low Plk4 levels are usually the limiting factor for centriole assembly, overexpressing Asl induces centriole overduplication, suggesting that the scaffold protein may have an additional function besides Plk4 recruitment. Klebba and Galletta et al. found that overexpressing Asl's C-terminal domain inhibited Plk4 turnover and induced centriole ampli-fi cation in Drosophila S2 cells. This region of the protein contained a second binding site for Plk4, and mutating this site eliminated Asl's ability to promote centriole duplication. Both the N-and C-terminal binding sites helped Asl form an oligomeric complex with Plk4 that stabilized the kinase during mitosis. In interphase cells, however, Asl's N-terminal domain facilitated Plk4's turnover by promoting the kinase's dimerization and autophosphorylation. The authors now want to investigate how Asl is regulated throughout the cell cycle and how the stable Asl–Plk4 complexes are organized on the surface of centrioles. Fennell et al. reveal that centromeres can stand in for telomeres and promote assembly of the fission yeast meiotic spindle. During meiotic prophase, the telo-meres of fi ssion yeast chromosomes cluster at the nuclear envelope. This " telomere bouquet " connects, via the inner nuclear membrane SUN protein Sad1, to the spindle pole body (SPB), the yeast equivalent of the centrosome. Mutant yeast unable to form a telomere bouquet have problems inserting their SPBs into the nuclear envelope so that they can form a bipolar meiotic spindle. Around half of these bouquet-defi cient yeast still manage to form a spindle, however, so Fennell et al. examined how these cells cope in the absence of telomere–SPB contacts. The researchers discovered that bouquet-defi cient cells could successfully assemble bipolar spindles if their centromeres contacted the SPB during meiotic prophase. Boosting centromere– SPB contacts completely restored meiotic spindle assembly in all bouquet-deficient cells. In contrast, forcing noncentro-meric chromatin regions to …

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عنوان ژورنال:

دوره 208  شماره 

صفحات  -

تاریخ انتشار 2015