Depletion of the Origin Recognition Complex Subunits Delays Aging in Budding Yeast
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 origin...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-04-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/8/1252 |
| _version_ | 1797436426114039808 |
|---|---|
| author | Karolina Stępień Adrianna Skoneczna Monika Kula-Maximenko Łukasz Jurczyk Mateusz Mołoń |
| author_facet | Karolina Stępień Adrianna Skoneczna Monika Kula-Maximenko Łukasz Jurczyk Mateusz Mołoń |
| author_sort | Karolina Stępień |
| collection | DOAJ |
| description | 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 <i>ORC</i> genes in the BY4743 background. Cells with only one copy of the <i>ORC</i> genes showed a significant decrease in the level of <i>ORC</i> 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 <i>ORC/orcΔ</i> 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. |
| first_indexed | 2024-03-09T11:02:30Z |
| format | Article |
| id | doaj.art-c0fb8e81e95e41e6a4de5eb07a1dba72 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T11:02:30Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-c0fb8e81e95e41e6a4de5eb07a1dba722023-12-01T01:12:35ZengMDPI AGCells2073-44092022-04-01118125210.3390/cells11081252Depletion of the Origin Recognition Complex Subunits Delays Aging in Budding YeastKarolina Stępień0Adrianna Skoneczna1Monika Kula-Maximenko2Łukasz Jurczyk3Mateusz Mołoń4Department of Biology, Institute of Biology and Biotechnology, University of Rzeszów, 35-601 Rzeszów, PolandInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, PolandThe Franciszek Górski Institute of Plant Physiology, Polish Academy of Sciences, 30-239 Krakow, PolandInstitute of Agricultural Sciences, Land Management and Environmental Protection, University of Rzeszow, 35-601 Rzeszów, PolandDepartment of Biology, Institute of Biology and Biotechnology, University of Rzeszów, 35-601 Rzeszów, PolandPrecise 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 <i>ORC</i> genes in the BY4743 background. Cells with only one copy of the <i>ORC</i> genes showed a significant decrease in the level of <i>ORC</i> 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 <i>ORC/orcΔ</i> 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.https://www.mdpi.com/2073-4409/11/8/1252agingcell cyclelifespanORCreplicationyeast |
| spellingShingle | Karolina Stępień Adrianna Skoneczna Monika Kula-Maximenko Łukasz Jurczyk Mateusz Mołoń Depletion of the Origin Recognition Complex Subunits Delays Aging in Budding Yeast Cells aging cell cycle lifespan ORC replication yeast |
| title | Depletion of the Origin Recognition Complex Subunits Delays Aging in Budding Yeast |
| title_full | Depletion of the Origin Recognition Complex Subunits Delays Aging in Budding Yeast |
| title_fullStr | Depletion of the Origin Recognition Complex Subunits Delays Aging in Budding Yeast |
| title_full_unstemmed | Depletion of the Origin Recognition Complex Subunits Delays Aging in Budding Yeast |
| title_short | Depletion of the Origin Recognition Complex Subunits Delays Aging in Budding Yeast |
| title_sort | depletion of the origin recognition complex subunits delays aging in budding yeast |
| topic | aging cell cycle lifespan ORC replication yeast |
| url | https://www.mdpi.com/2073-4409/11/8/1252 |
| work_keys_str_mv | AT karolinastepien depletionoftheoriginrecognitioncomplexsubunitsdelaysaginginbuddingyeast AT adriannaskoneczna depletionoftheoriginrecognitioncomplexsubunitsdelaysaginginbuddingyeast AT monikakulamaximenko depletionoftheoriginrecognitioncomplexsubunitsdelaysaginginbuddingyeast AT łukaszjurczyk depletionoftheoriginrecognitioncomplexsubunitsdelaysaginginbuddingyeast AT mateuszmołon depletionoftheoriginrecognitioncomplexsubunitsdelaysaginginbuddingyeast |