ArticlePLoS genetics2011
Multiple regulatory mechanisms to inhibit untimely initiation of DNA replication are important for stable genome maintenance.
Article in PLoS genetics, 2011. 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, 37 citations in OpenAlex.
- Unscheduled DNA replication in G1 causes genome instability and damage signatures indicative of replication collisions.Nature communications · 2022Article
- The Role of MTBP as a Replication Origin Firing Factor.Biology · 2022Review
- Refining the domain architecture model of the replication origin firing factor Treslin/TICRR.Life science alliance · 2022Article
- MTBP phosphorylation controls DNA replication origin firing.Scientific reports · 2021Article
- Isolation and analysis of rereplicated DNA by Rerep-Seq.Nucleic acids research · 2020Article
- Review
- Control of Eukaryotic DNA Replication Initiation-Mechanisms to Ensure Smooth Transitions.Genes · 2019Review
- Article
- Review
- The Intra-S Checkpoint Responses to DNA Damage.Genes · 2017Review
- A reconstituted system reveals how activating and inhibitory interactions control DDK dependent assembly of the eukaryotic replicative helicase.Nucleic acids research · 2015Article
- Evolutionary conservation of the CDK targets in eukaryotic DNA replication initiation.Chromosoma · 2015Review
- Helicase activation and establishment of replication forks at chromosomal origins of replication.Cold Spring Harbor perspectives in biology · 2013Review
- Efficient initiation of DNA replication in eukaryotes requires Dpb11/TopBP1-GINS interaction.Molecular and cellular biology · 2013Article
- Endogenous DNA replication stress results in expansion of dNTP pools and a mutator phenotype.The EMBO journal · 2012Article
- Separation of DNA replication from the assembly of break-competent meiotic chromosomes.PLoS genetics · 2012Article
- Broader utilization of origins of DNA replication in cancer cell lines along a 78 kb region of human chromosome 2q34.Journal of cellular biochemistry · 2012Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genomic instability is a hallmark of human cancer cells. To prevent genomic instability, chromosomal DNA is faithfully duplicated in every cell division cycle, and eukaryotic cells have complex regulatory mechanisms to achieve this goal. Here, we show that untimely activation of replication origins during the G1 phase is genotoxic and induces genomic instability in the budding yeast Saccharomyces cerevisiae. Our data indicate that cells preserve a low level of the initiation factor Sld2 to prevent untimely initiation during the normal cell cycle in addition to controlling the phosphorylation of Sld2 and Sld3 by cyclin-dependent kinase. Although untimely activation of origin is inhibited on multiple levels, we show that deregulation of a single pathway can cause genomic instability, such as gross chromosome rearrangements (GCRs). Furthermore, simultaneous deregulation of multiple pathways causes an even more severe phenotype. These findings highlight the importance of having multiple inhibitory mechanisms to prevent the untimely initiation of chromosome replication to preserve stable genome maintenance over generations in eukaryotes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.