ArticleThe Journal of cell biology2021
LRR1-mediated replisome disassembly promotes DNA replication by recycling replisome components.
Article in The Journal of cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Noncoding RNA Transcripts Based Molecular Phenotyping of MASLD and MASH Patients.Liver international communications · 2026Article
- Integrative Bulk and Single-Cell Transcriptome Profiling of Telomere-Related Genes Reveals a Robust Prognostic Signature and Immunotherapeutic Landscape in Neuroblastoma.Journal of Cancer · 2026Article
- The DNA replication machinery transmits dual signals to prevent unscheduled licensing and execution of centrosome duplication.Nature communications · 2025Article
- DNA polymerase α/primase extraction from chromatin by VCP/p97 restricts ATR activation during unperturbed DNA replication.Nature communications · 2025Article
- USP37 prevents unscheduled replisome unloading through MCM complex deubiquitination.Nature communications · 2025Article
- DNA replication recruits a friend to overcome a challenging break-up.The EMBO journal · 2024Article
- CMG helicase disassembly is essential and driven by two pathways in budding yeast.The EMBO journal · 2024Article
- Characterizing replisome disassembly in human cells.iScience · 2024Article
- Article
- The SPATA5-SPATA5L1 ATPase complex directs replisome proteostasis to ensure genome integrity.Cell · 2024Article
- Review
- Quantity and quality of minichromosome maintenance protein complexes couple replication licensing to genome integrity.Communications biology · 2024Review
- Genome maintenance meets mechanobiology.Chromosoma · 2024Review
- Cooperative assembly of p97 complexes involved in replication termination.Nature communications · 2022Article
- Structure of CRL2Lrr1, the E3 ubiquitin ligase that promotes DNA replication termination in vertebrates.Nucleic acids research · 2021Article
- Ubiquitin and SUMO pathways in DNA replication and replication-coupled repair.Critical reviews in biochemistry and molecular biologyReview
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
After two converging DNA replication forks meet, active replisomes are disassembled and unloaded from chromatin. A key process in replisome disassembly is the unloading of CMG helicases (CDC45-MCM-GINS), which is initiated in Caenorhabditis elegans and Xenopus laevis by the E3 ubiquitin ligase CRL2LRR1. Here, we show that human cells lacking LRR1 fail to unload CMG helicases and accumulate increasing amounts of chromatin-bound replisome components as cells progress through S phase. Markedly, we demonstrate that the failure to disassemble replisomes reduces the rate of DNA replication increasingly throughout S phase by sequestering rate-limiting replisome components on chromatin and blocking their recycling. Continued binding of CMG helicases to chromatin during G2 phase blocks mitosis by activating an ATR-mediated G2/M checkpoint. Finally, we provide evidence that LRR1 is an essential gene for human cell division, suggesting that CRL2LRR1 enzyme activity is required for the proliferation of cancer cells and is thus a potential target for cancer therapy.
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Registered trials
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.