Koyama Hirofumi, Itoh Masayuki, Miyahara Kohji, Tsuchiya Eiko
Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Kagamiyama, Higashi-Hiroshima, Japan.
FEBS Lett. 2002 Nov 6;531(2):215-21. doi: 10.1016/s0014-5793(02)03504-4.
The essential Nps1p/Sth1p is a catalytic subunit of the nucleosome-remodeling complex, RSC, of Saccharomyces cerevisiae that can alter nucleosome structure by using the energy of ATP hydrolysis. Besides the ATPase domain, Nps1p harbors the bromodomain, of which the function(s) have not yet been defined. We have isolated a temperature-sensitive mutant allele of NPS1, nps1-13, which has amino acid substitutions within the bromodomain. This mutation perturbed the interaction between the RSC components and enhanced the sensitivity of the cells to several DNA-damaging treatments at the permissive temperature. Reduced expression of NPS1 also caused DNA damage sensitivity. These results suggest the importance of the Nps1p bromodomain in RSC integrity and a model in which high amounts of RSC would be required for the cells to overcome DNA damage.
必需的Nps1p/Sth1p是酿酒酵母核小体重塑复合物RSC的催化亚基，它可以利用ATP水解的能量改变核小体结构。除了ATP酶结构域外，Nps1p还含有溴结构域，其功能尚未明确。我们分离出了NPS1的一个温度敏感突变等位基因nps1-13，该基因在溴结构域内有氨基酸替换。这种突变扰乱了RSC组件之间的相互作用，并增强了细胞在允许温度下对几种DNA损伤处理的敏感性。NPS1表达降低也会导致DNA损伤敏感性。这些结果表明Nps1p溴结构域在RSC完整性中的重要性，以及一个模型，即细胞需要大量的RSC来克服DNA损伤。
