ArticleProceedings of the National Academy of Sciences of the United States of America2017
MRG15-mediated tethering of PALB2 to unperturbed chromatin protects active genes from genotoxic stress.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 60 citations in OpenAlex.
- Tumor-targeted top1 inhibitor delivery with optimized parp inhibition in advanced solid tumors: a phase i trial of gapped scheduling.Nature communications · 2025Trial
- piR-26681 suppresses ovarian cancer progression by enhancing METTL3/METTL14-mediated mCellular & molecular biology letters · 2026Article
- MORF4L1 regulation and its role in chromatin remodeling, DNA damage, cellular senescence, and cardiometabolic disease.Vascular pharmacology · 2026Review
- EpGAT: integrating epigenetics and 3D genome structure to predict alternative splicing and polyadenylation.Briefings in bioinformatics · 2026Article
- PALB2 and 53BP1 govern post-resection homologous recombination DNA repair.Molecular cell · 2025Article
- Mono-ubiquitination of TopBP1 by PHRF1 enhances ATR activation and genomic stability.Nucleic acids research · 2025Article
- The homologous recombination factors BRCA2 and PALB2 interplay with mismatch repair pathways to maintain centromere stability and cell viability.Cell reports · 2025Article
- The strand exchange domain of tumor suppressor PALB2 is intrinsically disordered and promotes oligomerization-dependent DNA compaction.iScience · 2024Article
- Distinct mobility patterns of BRCA2 molecules at DNA damage sites.Nucleic acids research · 2024Article
- The strand exchange domain of tumor suppressor PALB2 is intrinsically disordered and promotes oligomerization-dependent DNA compaction.bioRxiv : the preprint server for biology · 2024Article
- Structural and functional insights into the epigenetic regulator MRG15.Acta pharmacologica Sinica · 2024Review
- PALB2-mutated human mammary cells display a broad spectrum of morphological and functional abnormalities induced by increased TGFβ signaling.Cellular and molecular life sciences : CMLS · 2024Article
- SIN-3 acts in distinct complexes to regulate the germline transcriptional program in Caenorhabditis elegans.Development (Cambridge, England) · 2023Article
- The SETD2 Methyltransferase Supports Productive HPV31 Replication through the LEDGF/CtIP/Rad51 Pathway.Journal of virology · 2023Article
- KAT2-mediated acetylation switches the mode of PALB2 chromatin association to safeguard genome integrity.eLife · 2022Article
- BRCA1-Dependent and Independent Recruitment of PALB2-BRCA2-RAD51 in the DNA Damage Response and Cancer.Cancer research · 2022Review
- Functional assessment of missense variants of uncertain significance in the cancer susceptibility gene PALB2.NPJ breast cancer · 2022Article
- Structural and functional specificity of H3K36 methylation.Epigenetics & chromatin · 2022Review
- The Chromatin Landscape Channels DNA Double-Strand Breaks to Distinct Repair Pathways.Frontiers in cell and developmental biology · 2022Review
- Article
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Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
Abstract
The partner and localiser of BRCA2 (PALB2) plays important roles in the maintenance of genome integrity and protection against cancer. Although PALB2 is commonly described as a repair factor recruited to sites of DNA breaks, recent studies provide evidence that PALB2 also associates with unperturbed chromatin. Here, we investigated the previously poorly described role of chromatin-associated PALB2 in undamaged cells. We found that PALB2 associates with active genes through its major binding partner, MRG15, which recognizes histone H3 trimethylated at lysine 36 (H3K36me3) by the SETD2 methyltransferase. Missense mutations that ablate PALB2 binding to MRG15 confer elevated sensitivity to the topoisomerase inhibitor camptothecin (CPT) and increased levels of aberrant metaphase chromosomes and DNA stress in gene bodies, which were suppressed by preventing DNA replication. Remarkably, the level of PALB2 at genic regions was frequently decreased, rather than increased, upon CPT treatment. We propose that the steady-state presence of PALB2 at active genes, mediated through the SETD2/H3K36me3/MRG15 axis, ensures an immediate response to DNA stress and therefore effective protection of these regions during DNA replication. This study provides a conceptual advance in demonstrating that the constitutive chromatin association of repair factors plays a key role in the maintenance of genome stability and furthers our understanding of why PALB2 defects lead to human genome instability syndromes.
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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.