ArticleMolecular cell2020
PCAF-Mediated Histone Acetylation Promotes Replication Fork Degradation by MRE11 and EXO1 in BRCA-Deficient Cells.
Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 73 citations in OpenAlex.
- Hierarchies of resistance to DNA damage response inhibitors: from pathway restoration to replication stress tolerance.Experimental hematology & oncology · 2026Review
- KAT2B-mediated epigenetic suppression of RAD51C enhances olaparib sensitivity in colorectal cancer.Cancer chemotherapy and pharmacology · 2026Article
- Histone lactylation increases CXCL1 expression for neutrophil infiltration and immune escape in pancreatic cancer.Nature communications · 2026Article
- Acetylation Regulates ACSL4 Degradation Through Chaperone-Mediated Autophagy to Alleviate Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integration of single-cell sequencing, transcriptome sequencing, and machine learning for constructing and validating histone acetylation-related prognostic risk models in hepatocellular carcinoma.Frontiers in immunology · 2026Article
- A recurrent pathogenic BRCA2 truncating variant reveals a role for BRCA2-PCAF complex in modulating NF-κB-driven transcription.Nature communications · 2025Article
- Decoding replication stress responses through post-translational modifications.Nature chemical biology · 2025Review
- PCAF-mediated acetylation regulates RAD51 dynamic localization on chromatin during HR repair.EMBO reports · 2025Article
- TRIM24 directs replicative stress responses to maintain ALT telomeres via chromatin signaling.Molecular cell · 2025Article
- Interleukin-33 Knockout Promotes High Mobility Group Box 1 Release from Astrocytes by Acetylation Mediated by P300/CBP-Associated Factor in Experimental Autoimmune Encephalomyelitis.Neuroscience bulletin · 2025Article
- Depletion of BRD9-mediated R-loop accumulation inhibits leukemia cell growth via transcription-replication conflict.Nucleic acids research · 2025Article
- Histone acetylation modulators in breast cancer.Breast cancer research : BCR · 2025Review
- PARP inhibition-associated heterochromatin confers increased DNA replication stress and vulnerability to ATR inhibition in SMARCA4-deficient cells.Cell death discovery · 2025Article
- Post-Translational Modifications of Proteins Orchestrate All Hallmarks of Cancer.Life (Basel, Switzerland) · 2025Review
- Acetylation-Mediated Epigenetic Consequences for Biological Control and Cancer.Results and problems in cell differentiation · 2025Review
- UFL1 triggers replication fork degradation by MRE11 in BRCA1/2-deficient cells.Nature chemical biology · 2024Article
- Histone H4 acetylation differentially modulates proliferation in adult oligodendrocyte progenitors.The Journal of cell biology · 2024Article
- PCAF promotes R-loop resolution via histone acetylation.Nucleic acids research · 2024Article
- A RAD18-UBC13-PALB2-RNF168 axis mediates replication fork recovery in BRCA1-deficient cancer cells.Nucleic acids research · 2024Article
- KDM6A-SND1 interaction maintains genomic stability by protecting the nascent DNA and contributes to cancer chemoresistance.Nucleic acids research · 2024Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Stabilization of stalled replication forks is a prominent mechanism of PARP (Poly(ADP-ribose) Polymerase) inhibitor (PARPi) resistance in BRCA-deficient tumors. Epigenetic mechanisms of replication fork stability are emerging but remain poorly understood. Here, we report the histone acetyltransferase PCAF (p300/CBP-associated) as a fork-associated protein that promotes fork degradation in BRCA-deficient cells by acetylating H4K8 at stalled replication forks, which recruits MRE11 and EXO1. A H4K8ac binding domain within MRE11/EXO1 is required for their recruitment to stalled forks. Low PCAF levels, which we identify in a subset of BRCA2-deficient tumors, stabilize stalled forks, resulting in PARPi resistance in BRCA-deficient cells. Furthermore, PCAF activity is tightly regulated by ATR (ataxia telangiectasia and Rad3-related), which phosphorylates PCAF on serine 264 (S264) to limit its association and activity at stalled forks. Our results reveal PCAF and histone acetylation as critical regulators of fork stability and PARPi responses in BRCA-deficient cells, which provides key insights into targeting BRCA-deficient tumors and identifying epigenetic modulators of chemotherapeutic responses.
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