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Published on: March 7, 2019
Isolation of two genes that affect mitotic chromosome transmission in S. cerevisiae
Abstract:
Two DNA sequences that reduce mitotic fidelity of chromosome transmission have been identified: MIF1 and MIF2. MIF1 is a unique sequence located on the right arm of chromosome XII that stimulates loss and recombination for both chromosomes V and VII when present in a high copy number plasmid. MIF1 is not essential for cell division but is necessary for the normal fidelity of chromosome transmission. MIF2 is a unique sequence located 15 cM distal to HIS6 on chromosome IX that induces a high frequency of chromosome VII loss and a lower frequency of chromosome V loss when present in high copy number; it has no effect on mitotic recombination. Disruption of the genomic MIF2 locus was lethal and cells lacking this function arrested division with a terminal phenotype characteristic of a block in DNA replication or nuclear division.
Insights
Two DNA sequences, MIF1 and MIF2, were identified that decrease chromosome transmission accuracy during cell division. MIF1 increases chromosome loss and recombination, while MIF2 disruption is lethal, highlighting their roles in maintaining genomic stability.
Area of Science:
- Genetics
- Molecular Biology
- Cell Biology
Background:
- Mitotic fidelity, the accurate transmission of chromosomes during cell division, is crucial for genomic stability.
- Defects in mitotic fidelity can lead to aneuploidy and diseases such as cancer.
- Understanding the genetic factors that influence mitotic fidelity is essential for comprehending cellular health and disease.
Purpose of the Study:
- To identify and characterize DNA sequences that impact the fidelity of chromosome transmission during mitosis.
- To investigate the specific roles of two newly identified sequences, MIF1 and MIF2, in chromosome segregation and stability.
Main Methods:
- Utilized high copy number plasmid systems to study the effects of MIF1 and MIF2 on chromosome V and VII transmission.
- Assessed chromosome loss and mitotic recombination frequencies in yeast strains containing these plasmids.
- Investigated the consequences of disrupting the genomic MIF2 locus, including cell viability and division phenotypes.
Main Results:
- MIF1, when overexpressed on a plasmid, stimulates both chromosome loss and recombination for chromosomes V and VII.
- MIF1 is not essential for cell division but is required for normal chromosome transmission fidelity.
- MIF2, when overexpressed on a plasmid, induces high frequency of chromosome VII loss and lower frequency of chromosome V loss, without affecting mitotic recombination.
- Genomic disruption of MIF2 was lethal, causing cells to arrest with a phenotype indicative of blocked DNA replication or nuclear division.
Conclusions:
- MIF1 and MIF2 are distinct DNA sequences that play significant roles in maintaining mitotic chromosome transmission fidelity.
- MIF1 appears to influence both chromosome segregation and recombination, whereas MIF2 is essential for viability and proper nuclear division, potentially through a role in DNA replication or segregation.
- These findings contribute to understanding the genetic control of chromosome stability and the consequences of its disruption.
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