Prichard Amy, Johansson Marnie, Kirkpatrick David T, Clarke Duncan J
Department of Genetics, Cell Biology & Development, University of Minnesota, Minneapolis, MN, USA.
bioRxiv. 2024 Dec 11:2024.12.09.627563. doi: 10.1101/2024.12.09.627563.
Histone tail phosphorylation has diverse effects on a myriad of cellular processes, including cell division, and is highly conserved throughout eukaryotes. Histone H3 phosphorylation at threonine 3 (H3T3) during mitosis occurs at the inner centromeres and is required for proper biorientation of chromosomes on the mitotic spindle. While H3T3 is also phosphorylated during meiosis, a possible role for this modification has not been tested. Here, we asked if H3T3 phosphorylation (H3T3ph) is important for meiotic division by quantifying sporulation efficiency and spore viability in mutants with a T3A amino acid substitution. The T3A substitution resulted in greatly reduced sporulation efficiency and reduced spore viability. Analysis of two other H3 tail mutants, K4A and S10A, revealed different effects on sporulation efficiency and spore viability compared to the T3A mutant, suggesting that these phenotypes are due to failures in distinct functions. To determine if the spindle checkpoint promotes spore viability of the T3A mutant, the gene required for the spindle assembly checkpoint was deleted to abolish spindle assembly checkpoint function. This resulted in a severe reduction in spore viability following meiosis. Altogether, the data reveal a critical function for histone H3 threonine 3 that requires monitoring by the spindle checkpoint to ensure successful completion of meiosis.
组蛋白尾部磷酸化对包括细胞分裂在内的众多细胞过程具有多种影响,并且在整个真核生物中高度保守。有丝分裂期间,组蛋白H3苏氨酸3位点(H3T3)的磷酸化发生在内着丝粒,是染色体在有丝分裂纺锤体上正确双定向所必需的。虽然减数分裂期间H3T3也会发生磷酸化,但这种修饰的可能作用尚未得到验证。在这里,我们通过量化T3A氨基酸替代突变体中的孢子形成效率和孢子活力,来探究H3T3磷酸化(H3T3ph)对减数分裂是否重要。T3A替代导致孢子形成效率大幅降低和孢子活力下降。对另外两个H3尾部突变体K4A和S10A的分析显示,与T3A突变体相比,它们对孢子形成效率和孢子活力有不同影响,这表明这些表型是由于不同功能的失败所致。为了确定纺锤体检查点是否促进T3A突变体的孢子活力,删除了纺锤体组装检查点所需的 基因以消除纺锤体组装检查点功能。这导致减数分裂后孢子活力严重下降。总之,这些数据揭示了组蛋白H3苏氨酸3的关键功能,该功能需要纺锤体检查点进行监测以确保减数分裂成功完成。