Department of Biochemistry and Cell Biology, Institute of Biology and Biotechnology, University of Rzeszow, 35-601 Rzeszow, Poland.
Laboratory of Yeast Molecular Genetics, Institute of Molecular Biology "Acad. R. Tsanev", Bulgarian Academy of Sciences, 1123 Sofia, Bulgaria.
Cells. 2022 Sep 3;11(17):2754. doi: 10.3390/cells11172754.
Ageing is accompanied by dramatic changes in chromatin structure organization and genome function. Two essential components of chromatin, the linker histone Hho1p and actin-related protein 4 (Arp4p), have been shown to physically interact in cells, thus maintaining chromatin dynamics and function, as well as genome stability and cellular morphology. Disrupting this interaction has been proven to influence the stability of the yeast genome and the way cells respond to stress during chronological ageing. It has also been proven that the abrogated interaction between these two chromatin proteins elicited premature ageing phenotypes. Alterations in chromatin compaction have also been associated with replicative ageing, though the main players are not well recognized. Based on this knowledge, here, we examine how the interaction between Hho1p and Arp4p impacts the ageing of mitotically active yeast cells. For this purpose, two sets of strains were used-haploids (WT(n), , and ) and their heterozygous diploid counterparts (WT(2n), /, / and /)-for the performance of extensive morphological and physiological analyses during replicative ageing. These analyses included a comparative examination of the yeast cells' chromatin structure, proliferative and reproductive potential, and resilience to stress, as well as polysome profiles and chemical composition. The results demonstrated that the haploid chromatin mutants and demonstrated a significant reduction in replicative and total lifespan. These findings lead to the conclusion that the importance of a healthy interaction between Arp4p and Hho1p in replicative ageing is significant. This is proof of the concomitant importance of Hho1p and Arp4p in chronological and replicative ageing.
衰老伴随着染色质结构组织和基因组功能的巨大变化。染色质的两个基本组成部分，连接组蛋白 Hho1p 和肌动蛋白相关蛋白 4（Arp4p），已被证明在细胞中物理相互作用，从而维持染色质动力学和功能，以及基因组稳定性和细胞形态。事实证明，破坏这种相互作用会影响酵母基因组的稳定性以及细胞在生物钟衰老过程中应对压力的方式。还证明了这两种染色质蛋白之间的相互作用被削弱会引发过早衰老表型。染色质紧缩的改变也与复制性衰老有关，尽管主要参与者尚未得到很好的认可。基于这些知识，我们在这里研究 Hho1p 和 Arp4p 之间的相互作用如何影响有丝分裂活性酵母细胞的衰老。为此，我们使用了两组菌株——单倍体（WT(n)、 、 和 ）及其杂合二倍体对应物（WT(2n)、/、/ 和 /）——在复制性衰老过程中进行广泛的形态和生理分析。这些分析包括比较检查酵母细胞的染色质结构、增殖和生殖潜力以及对压力的恢复能力，以及多核糖体图谱和化学成分。结果表明，单倍体染色质突变体 和 在复制和总寿命方面显著缩短。这些发现得出的结论是，Arp4p 和 Hho1p 之间健康相互作用在复制性衰老中的重要性。这证明了 Hho1p 和 Arp4p 在生物钟和复制性衰老中的伴随重要性。
