Hayashi Takeshi, Teruya Takayuki, Chaleckis Romanas, Morigasaki Susumu, Yanagida Mitsuhiro
G0 Cell Unit, Okinawa Institute of Science and Technology Graduate University, Onna-son, Okinawa 904-0495, Japan.
G0 Cell Unit, Okinawa Institute of Science and Technology Graduate University, Onna-son, Okinawa 904-0495, Japan.
iScience. 2018 Jul 27;5:38-51. doi: 10.1016/j.isci.2018.06.011. Epub 2018 Jun 30.
S-adenosylmethionine is an important compound, because it serves as the methyl donor in most methyl transfer reactions, including methylation of proteins, nucleic acids, and lipids. However, cellular defects in the genetic disruption of S-adenosylmethionine synthesis are not well understood. Here, we report the isolation and characterization of temperature-sensitive mutants of fission yeast S-adenosylmethionine synthetase (Sam1). Levels of S-adenosylmethionine and methylated histone H3 were greatly diminished in sam1 mutants. sam1 mutants stopped proliferating in vegetative culture and arrested specifically in G2 phase without cell elongation. Furthermore, sam1 mutants lost viability during nitrogen starvation-induced G0 phase quiescence. After release from the G0 state, sam1 mutants could neither increase in cell size nor re-initiate DNA replication in the rich medium. Sam1 is thus required for cell growth and proliferation, and maintenance of and exit from quiescence. sam1 mutants lead to broad cellular and drug response defects, as expected, since S. pombe contains more than 90 S-adenosylmethionine-dependent methyltransferases.
S-腺苷甲硫氨酸是一种重要的化合物,因为它在大多数甲基转移反应中作为甲基供体,包括蛋白质、核酸和脂质的甲基化反应。然而,S-腺苷甲硫氨酸合成基因破坏中的细胞缺陷尚未得到充分了解。在此,我们报告了裂殖酵母S-腺苷甲硫氨酸合成酶(Sam1)温度敏感突变体的分离和表征。在sam1突变体中,S-腺苷甲硫氨酸和甲基化组蛋白H3的水平大幅降低。sam1突变体在营养培养中停止增殖,并特异性地停滞在G2期,细胞不伸长。此外,sam1突变体在氮饥饿诱导的G0期静止期间丧失活力。从G0状态释放后,sam1突变体在丰富培养基中既不能增大细胞大小,也不能重新启动DNA复制。因此,Sam1是细胞生长、增殖以及维持静止和退出静止所必需的。正如预期的那样,sam1突变体导致广泛的细胞和药物反应缺陷,因为粟酒裂殖酵母含有90多种依赖S-腺苷甲硫氨酸的甲基转移酶。