ArticleCell cycle (Georgetown, Tex.)2008
DNA replication in early S phase pauses near newly activated origins.
Article in Cell cycle (Georgetown, Tex.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Mutant p53 establishes targetable tumor dependency by promoting unscheduled replication.The Journal of clinical investigation · 2017Article
- The hunt for origins of DNA replication in multicellular eukaryotes.F1000prime reports · 2015Review
- The human oncoprotein MDM2 induces replication stress eliciting early intra-S-phase checkpoint response and inhibition of DNA replication origin firing.Nucleic acids research · 2014Article
- Use of the DNA fiber spreading technique to detect the effects of mutant p53 on DNA replication.Methods in molecular biology (Clifton, N.J.) · 2013Article
- Temporal and functional analysis of DNA replicated in early S phase.Advances in enzyme regulation · 2011Review
- BRG1 co-localizes with DNA replication factors and is required for efficient replication fork progression.Nucleic acids research · 2010Article
- Abasic sites preferentially form at regions undergoing DNA replication.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2010Article
- Temporal differences in DNA replication during the S phase using single fiber analysis of normal human fibroblasts and glioblastoma T98G cells.Cell cycle (Georgetown, Tex.) · 2009Article
- Fragile genomic sites are associated with origins of replication.Genome biology and evolution · 2009Article
- Divergent S phase checkpoint activation arising from prereplicative complex deficiency controls cell survival.Molecular biology of the cell · 2009Article
- DNA replication and the GINS complex: localization on extended chromatin fibers.Epigenetics & chromatin · 2009Article
- DNA damage checkpoint responses in the S phase of synchronized diploid human fibroblasts.Photochemistry and photobiologyArticle
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Authors and funding
5 authors.
Funding
Abstract
During the S phase of the cell cycle, the entire genome is replicated. There is a high level of orderliness to this process through the temporally and topologically coordinated activation of many replication origins situated along chromosomes. We investigated the program of replication from origins initiating in early S phase by labeling synchronized normal human fibroblasts (NHF1) with nucleotide analogs for various pulse times and measuring labeled tracks in combed DNA fibers. Our analysis showed that replication forks progress 9-35 kilobases from newly initiated origins, followed by a pause in synthesis before replication resumes. Pausing was not observed near origins that initiated in the middle of S phase. No evidence for pausing near origins was found at the beginning of the S phase in glioblastoma T98G cells. Treatment with the S phase checkpoint inhibitor caffeine abrogated pausing in NHF1 cells in early S phase. This suggests that pausing may comprise a novel aspect of the intra-S phase checkpoint pathway or a related new early S checkpoint. Further, it is possible that the loss of this regulatory process in cancer cells such as T98G could be a contributing factor in the genetic instability that typifies cancers.
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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.