ArticleScientific reports2018
PREP1 tumor suppressor protects the late-replicating DNA by controlling its replication timing and symmetry.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 22 citations in OpenAlex.
- Identification of key biomarkers and potential therapeutic drugs in nasopharyngeal carcinoma based on comprehensive bioinformatics analysis.Discover oncology · 2025Article
- Search for New Participants in the Pathogenesis of High-Grade Serous Ovarian Cancer with the Potential to Be Used as Diagnostic Molecules.Life (Basel, Switzerland) · 2022Article
- Comprehensive analysis of DNA replication timing across 184 cell lines suggests a role for MCM10 in replication timing regulation.Human molecular genetics · 2022Article
- The transcription factor PREP1(PKNOX1) regulates nuclear stiffness, the expression of LINC complex proteins and mechanotransduction.Communications biology · 2022Article
- PBX1: a key character of the hallmarks of cancer.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Mammalian DNA Replication Timing.Cold Spring Harbor perspectives in biology · 2021Review
- Replication Stress, Genomic Instability, and Replication Timing: A Complex Relationship.International journal of molecular sciences · 2021Review
- Mapping the native interaction surfaces of PREP1 with PBX1 by cross-linking mass-spectrometry and mutagenesis.Scientific reports · 2020Article
- Asymmetric histone inheritance via strand-specific incorporation and biased replication fork movement.Nature structural & molecular biology · 2019Article
- PKNOX1 acts as a transcription factor of DHH and promotes the progression of stomach adenocarcinoma by regulating the Hedgehog signalling pathway.International journal of immunopathology and pharmacologyArticle
Corrections and comments
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Authors and funding
12 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The synthesis of middle-to-late-replicating DNA can be affected independently of the rest of the genome by down-regulating the tumor suppressor PREP1 (PKNOX1). Indeed, DNA combing shows that PREP1 down-regulation affects DNA replication rate, increases the number of simultaneously firing origins and the asymmetry of DNA replication, leading to DNA damage. Genome-wide analysis of replication timing by Repli-seq shows that, upon PREP1 down-regulation, 25% of the genome is replicated earlier in the S-phase. The targeted DNA sequences correspond to Lamin-Associated Domains (LADs), and include late-replicating (LRRs) and temporal transition regions (TTRs). Notably, the distribution of PREP1 DNA binding sites and of its target genes indicates that DNA replication defects are independent of the overall PREP1 transcriptional activity. Finally, PREP1 down-regulation causes a substantial decrease in Lamin B1 levels. This suggests that DNA is released from the nuclear lamina earlier than in the control cells and is available for replication, thus explaining timing defects and DNA damage.This is the first evidence that the replication timing of a specific fraction of the human genome is affected by PREP1 tumor suppressor. This previously unknown function might significantly contribute to the genomic instability observed in human tumors.
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