Depletion of the Origin Recognition Complex Subunits Delays Aging in Budding Yeast

Cells

Mateusz Mołoń¹  Karolina Stępień¹  Łukasz Jurczyk²  Adrianna Skoneczna³  Monika Kula-Maximenko⁴ 

[1]Department of Biology, Institute of Biology and Biotechnology, University of Rzeszów, 35-601 Rzeszów, Poland

[2]Institute of Agricultural Sciences, Land Management and Environmental Protection, University of Rzeszow, 35-601 Rzeszów, Poland

[3]Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland

[4]The Franciszek Górski Institute of Plant Physiology, Polish Academy of Sciences, 30-239 Krakow, Poland

关键词: aging;    cell cycle;    lifespan;    ORC;    replication;    yeast;   

DOI  :  10.3390/cells11081252

来源: DOAJ

【 摘 要 】

Precise DNA replication is pivotal for ensuring the accurate inheritance of genetic information. To avoid genetic instability, each DNA fragment needs to be amplified only once per cell cycle. DNA replication in eukaryotes starts with the binding of the origin recognition complex (ORC) to the origins of DNA replication. The genes encoding ORC subunits have been conserved across eukaryotic evolution and are essential for the initiation of DNA replication. In this study, we conducted an extensive physiological and aging-dependent analysis of heterozygous cells lacking one copy of ORC genes in the BY4743 background. Cells with only one copy of the ORC genes showed a significant decrease in the level of ORC mRNA, a delay in the G1 phase of the cell cycle, and an extended doubling time. Here, we also show that the reducing the levels of Orc1-6 proteins significantly extends both the budding and average chronological lifespans. Heterozygous ORC/orcΔ and wild-type diploid cells easily undergo haploidization during chronological aging. This ploidy shift might be related to nutrient starvation or the inability to survive under stress conditions. A Raman spectroscopy analysis helped us to strengthen the hypothesis of the importance of lipid metabolism and homeostasis in aging.

【 授权许可】

Unknown