Department of Applied Bioscience and Biotechnology, Faculty of Life and Environmental Science, Shimane University, Matsue 690-8504, Japan.
FEBS Lett. 2012 Nov 30;586(23):4190-6. doi: 10.1016/j.febslet.2012.10.020. Epub 2012 Oct 23.
An H3/H4 histone chaperone, Asf1, plays an essential role in maintaining genomic stability in many species, including fission yeast. Here, we showed that overexpression of a CENP-A chaperone Sim3 suppressed the temperature sensitive phenotype of asf1-33 and asf1-30 mutants and the defect in chromatin structure, and prevented the accumulation of DNA damage in asf1-33 mutants at high temperatures. Furthermore, asf1-33 and Δsim3 were synthetic lethal. Consistent with this, shutdown of sim3 expression in asf1-33 Δsim3 double mutants that contained extragenic sim3 resulted in growth retardation. In addition, the Δsim3 mutant displayed sensitivity to thiabendazol and hydroxyurea, which suggests that Sim3 plays a general role in maintaining chromatin structure. Our results suggest a possibility that Sim3 functions as a histone chaperone.
一种 H3/H4 组蛋白伴侣蛋白，ASF1，在许多物种中，包括裂殖酵母中，发挥着维持基因组稳定性的重要作用。在这里，我们表明，CENP-A 伴侣蛋白 Sim3 的过表达抑制了 asf1-33 和 asf1-30 突变体的温度敏感表型和染色质结构缺陷，并防止了 asf1-33 突变体在高温下 DNA 损伤的积累。此外，asf1-33 和 Δsim3 是合成致死的。与此一致的是，在包含外源性 sim3 的 asf1-33 Δsim3 双突变体中关闭 sim3 的表达导致生长迟缓。此外，Δsim3 突变体对噻苯达唑和羟基脲敏感，这表明 Sim3 在维持染色质结构方面发挥着一般作用。我们的结果表明，Sim3 作为组蛋白伴侣蛋白发挥作用的可能性。
