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

Stępień, Karolina and Skoneczna, Adrianna and Kula-Maximenko, Monika and Jurczyk, Łukasz and Mołoń, Mateusz (2022) Depletion of the Origin Recognition Complex Subunits Delays Aging in Budding Yeast. Cells, 11 (8). pp. 1252-1273. ISSN 2073-4409


Official URL: https://www.mdpi.com/2073-4409/11/8/1252


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.

Item Type:Article
Uncontrolled Keywords:aging; cell cycle; lifespan; ORC; replication; yeast
Subjects:Q Science > Q Science (General)
Q Science > QR Microbiology
ID Code:2279
Deposited By: dr hab. Adrianna Skoneczna
Deposited On:29 Jun 2023 14:04
Last Modified:29 Jun 2023 14:04

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