ArticlePLoS genetics2017
Defective replication initiation results in locus specific chromosome breakage and a ribosomal RNA deficiency in yeast.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Article
- Ribosomal DNA replication time coordinates completion of genome replication and anaphase in yeast.Cell reports · 2023Article
- Two differentially stable rDNA loci coexist on the same chromosome and form a single nucleolus.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Yeast ORC sumoylation status fine-tunes origin licensing.Genes & development · 2022Article
- High abundance of CDC45 inhibits cell proliferation through elevation of HSPA6.Cell proliferation · 2022Article
- Article
- Global genomic instability caused by reduced expression of DNA polymerase ε in yeast.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The S-Phase Cyclin Clb5 Promotes rRNA Gene (rDNA) Stability by Maintaining Replication Initiation Efficiency in rDNA.Molecular and cellular biology · 2021Article
- Identification andmicroPublication biology · 2021Article
- Meiotic gatekeeper STRA8 regulates cell cycle by interacting with SETD8 during spermatogenesis.Journal of cellular and molecular medicine · 2020Article
- Tissue-Specific DNA Replication Defects inGenetics · 2020Article
- The effects of manipulating levels of replication initiation factors on origin firing efficiency in yeast.PLoS genetics · 2019Article
- Phenotypic and Genotypic Consequences of CRISPR/Cas9 Editing of the Replication Origins in the rDNA ofGenetics · 2019Article
- The processivity factor Pol32 mediates nuclear localization of DNA polymerase delta and prevents chromosomal fragile site formation in Drosophila development.PLoS genetics · 2019Article
- Substitutions Are Boring: Some Arguments about Parallel Mutations and High Mutation Rates.Trends in genetics : TIG · 2019Review
- The peculiar genetics of the ribosomal DNA blurs the boundaries of transgenerational epigenetic inheritance.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2019Review
- Chromatin Remodeling Factors Isw2 and Ino80 Regulate Chromatin, Replication, and Copy Number of theGenetics · 2018Article
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6 authors.
Funding
Abstract
A form of dwarfism known as Meier-Gorlin syndrome (MGS) is caused by recessive mutations in one of six different genes (ORC1, ORC4, ORC6, CDC6, CDT1, and MCM5). These genes encode components of the pre-replication complex, which assembles at origins of replication prior to S phase. Also, variants in two additional replication initiation genes have joined the list of causative mutations for MGS (Geminin and CDC45). The identity of the causative MGS genetic variants strongly suggests that some aspect of replication is amiss in MGS patients; however, little evidence has been obtained regarding what aspect of chromosome replication is faulty. Since the site of one of the missense mutations in the human ORC4 alleles is conserved between humans and yeast, we sought to determine in what way this single amino acid change affects the process of chromosome replication, by introducing the comparable mutation into yeast (orc4Y232C). We find that yeast cells with the orc4Y232C allele have a prolonged S-phase, due to compromised replication initiation at the ribosomal DNA (rDNA) locus located on chromosome XII. The inability to initiate replication at the rDNA locus results in chromosome breakage and a severely reduced rDNA copy number in the survivors, presumably helping to ensure complete replication of chromosome XII. Although reducing rDNA copy number may help ensure complete chromosome replication, orc4Y232C cells struggle to meet the high demand for ribosomal RNA synthesis. This finding provides additional evidence linking two essential cellular pathways-DNA replication and ribosome biogenesis.
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