ArticleNature communications2022
Lagging strand gap suppression connects BRCA-mediated fork protection to nucleosome assembly through PCNA-dependent CAF-1 recycling.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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Who cites it
28 citing papers in PubMed, 31 citations in OpenAlex.
- An updated view on lagging strand DNA replication: implications for the replication stress response.Cell cycle (Georgetown, Tex.) · 2026Article
- Distinct functions of mammalian RAD51 paralogs in genome maintenance.Biochemical Society transactions · 2026Review
- g BRCA1 and g BRCA2 mutations in specific different domains affect ovarian cancer prognosis: A multicenter retrospective study.Chinese medical journal · 2026Article
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- Review
- XPF mediates 3' flap processing for FEN1-independent Okazaki fragment maturation.Nucleic acids research · 2026Article
- The nuclease EXO1 promotes genomic instability by degrading nascent DNA in BRCA-proficient cells.Nature communications · 2026Article
- Genome-wide CRISPR screens identify the EXO1-CAF-1 pathway suppressing R-loop-associated DNA damage.Nucleic acids research · 2026Article
- The expanding roles of homologous recombination proteins in genome stability.The EMBO journal · 2026Review
- Fork Reversal Safeguards Epigenetic Inheritance During Replication Stress.Research square · 2026Article
- XPF mediates 3' flap processing for FEN1-independent Okazaki fragment maturation.bioRxiv : the preprint server for biology · 2025Article
- Human TLS DNA polymerase: saviors or threats under replication stress?Molecular and cellular biochemistry · 2025Review
- Targeting BRCA1-deficient PARP inhibitor-resistant cells with nickases reveals nick resection as a cancer vulnerability.Nature cancer · 2025Article
- CAF-1 promotes efficient PrimPol recruitment to nascent DNA for single-stranded DNA gap formation.Nucleic acids research · 2024Article
- CRISPR knockout genome-wide screens identify the HELQ-RAD52 axis in regulating the repair of cisplatin-induced single-stranded DNA gaps.Nucleic acids research · 2024Article
- Positioning loss of PARP1 activity as the central toxic event in BRCA-deficient cancer.DNA repair · 2024Review
- SNF2L suppresses nascent DNA gap formation to promote DNA synthesis.Nucleic acids research · 2024Article
- DNA polymerase α-primase facilitates PARP inhibitor-induced fork acceleration and protects BRCA1-deficient cells against ssDNA gaps.Nature communications · 2024Article
- PARP10 promotes the repair of nascent strand DNA gaps through RAD18 mediated translesion synthesis.Nature communications · 2024Article
- BRCAness, DNA gaps, and gain and loss of PARP inhibitor-induced synthetic lethality.The Journal of clinical investigation · 2024Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The inability to protect stalled replication forks from nucleolytic degradation drives genome instability and underlies chemosensitivity in BRCA-deficient tumors. An emerging hallmark of BRCA-deficiency is the inability to suppress replication-associated single-stranded DNA (ssDNA) gaps. Here, we report that lagging strand ssDNA gaps interfere with the ASF1-CAF-1 nucleosome assembly pathway, and drive fork degradation in BRCA-deficient cells. We show that CAF-1 function at replication forks is lost in BRCA-deficient cells, due to defects in its recycling during replication stress. This CAF-1 recycling defect is caused by lagging strand gaps which preclude PCNA unloading, causing sequestration of PCNA-CAF-1 complexes on chromatin. Importantly, correcting PCNA unloading defects in BRCA-deficient cells restores CAF-1-dependent fork stability. We further show that the activation of a HIRA-dependent compensatory histone deposition pathway restores fork stability to BRCA-deficient cells. We thus define lagging strand gap suppression and nucleosome assembly as critical enablers of BRCA-mediated fork stability.
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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.