ArticleGenome biology2021
Transcription shapes DNA replication initiation to preserve genome integrity.
Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Decoding DNA metabolism and its clinical relevance through the lens of high-throughput sequencing assays.Medical review (2021) · 2026Review
- Slow RNAPII elongation enhances naive pluripotency rewiring while maintaining high replication fork speed.Science advances · 2026Article
- Multiple strategies to resolve the conflict between replication and transcription in mammalian cells.Nucleic acids research · 2026Article
- Interplay between cohesin and RNA polymerase II in regulating chromatin interactions and gene transcription.Nature structural & molecular biology · 2026Article
- OCT4 enhances the firing efficiency of late DNA replication origins in mouse embryonic stem cells.Nature communications · 2026Article
- A lethal ORC ATPase mutation is suppressed by alterations in ORC and RNA Pol II transcription components.PloS one · 2026Article
- Regulated TRESLIN-MTBP loading governs initiation zones and replication timing in human DNA replication.Nature communications · 2025Article
- Spatial mapping of DNA synthesis reveals dynamics and geometry of human replication nanostructures.The EMBO journal · 2025Article
- A mitotic bookmark coordinates transcription and replication in Drosophila embryos.Nucleic acids research · 2025Article
- Master transcription-factor binding sites constitute the core of early replication control elements.The EMBO journal · 2025Article
- Polymerase-usage sequencing identifies initiation zones with less bias across S phase in mouse embryonic stem cells.Journal of biochemistry · 2025Article
- The double life of mammalian DNA replication origins.Genes & development · 2025Review
- KMT2C/KMT2D-dependent H3K4me1 mediates changes in DNA replication timing and origin activity during a cell fate transition.Cell reports · 2025Article
- Dormant origin firing promotes head-on transcription-replication conflicts at transcription termination sites in response to BRCA2 deficiency.Nature communications · 2024Article
- A commentary of "Initial DNA melting in human DNA replication initiation": Top 10 Scientific Advances of 2023, China.Fundamental research · 2024Article
- The MCM2-7 Complex: Roles beyond DNA Unwinding.Biology · 2024Review
- MLL3/MLL4 enzymatic activity shapes DNA replication timing.bioRxiv : the preprint server for biology · 2023Article
- Transcription-Replication Conflicts as a Source of Genome Instability.Annual review of genetics · 2023Review
- Repli-seq Sample Preparation using Cell Sorting with Cell-Permeant Dyes.Current protocols · 2023Article
- Rac GTPase activating protein 1 promotes the glioma growth by regulating the expression of MCM3.Translational oncology · 2023Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEarly DNA replication occurs within actively transcribed chromatin compartments in mammalian cells, raising the immediate question of how early DNA replication coordinates with transcription to avoid collisions and DNA damage.
resultsWe develop a high-throughput nucleoside analog incorporation sequencing assay and identify thousands of early replication initiation zones in both mouse and human cells. The identified early replication initiation zones fall in open chromatin compartments and are mutually exclusive with transcription elongation. Of note, early replication initiation zones are mainly located in non-transcribed regions adjacent to transcribed regions. Mechanistically, we find that RNA polymerase II actively redistributes the chromatin-bound mini-chromosome maintenance complex (MCM), but not the origin recognition complex (ORC), to actively restrict early DNA replication initiation outside of transcribed regions. In support of this finding, we detect apparent MCM accumulation and DNA replication initiation in transcribed regions due to anchoring of nuclease-dead Cas9 at transcribed genes, which stalls RNA polymerase II. Finally, we find that the orchestration of early DNA replication initiation by transcription efficiently prevents gross DNA damage.
conclusionRNA polymerase II redistributes MCM complexes, but not the ORC, to prevent early DNA replication from initiating within transcribed regions. This RNA polymerase II-driven MCM redistribution spatially separates transcription and early DNA replication events and avoids the transcription-replication initiation collision, thereby providing a critical regulatory mechanism to preserve genome stability.
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