ArticleNucleic acids research2023
CRISPR screens in sister chromatid cohesion defective cells reveal PAXIP1-PAGR1 as regulator of chromatin association of cohesin.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 12 citations in OpenAlex.
- Rare genetic diseases associated with G-quadruplex-induced replication stress.Communications biology · 2026Review
- The expression of establishment of cohesion 1 homolog 2 (ESCO2) in tumor cells and its research progress as a therapeutic target.European journal of medical research · 2025Review
- Glucose-Responsive PAGR1-Regulated Skeletal Muscle Gene Program Controls Systemic Glucose Homeostasis and Hepatic Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cohesin in 3D: development, differentiation, and disease.Genes & development · 2025Review
- Co-essentiality analysis identifies PRR12 as a cohesin interacting protein and contributor to genomic integrity.Developmental cell · 2025Article
- Liquid condensates: a new barrier to loop extrusion?Cellular and molecular life sciences : CMLS · 2025Review
- ANKRD11 binding to cohesin suggests a connection between KBG syndrome and Cornelia de Lange syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis.The Journal of experimental medicine · 2025Article
- Review
- Competition shapes the landscape of X-chromosome-linked genetic diversity.Nature genetics · 2024Article
- Mapping of DDX11 genetic interactions defines sister chromatid cohesion as the major dependency.G3 (Bethesda, Md.) · 2024Article
- PAXIP1 and STAG2 converge to maintain 3D genome architecture and facilitate promoter/enhancer contacts to enable stress hormone-dependent transcription.Nucleic acids research · 2023Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
The cohesin complex regulates higher order chromosome architecture through maintaining sister chromatid cohesion and folding chromatin by DNA loop extrusion. Impaired cohesin function underlies a heterogeneous group of genetic syndromes and is associated with cancer. Here, we mapped the genetic dependencies of human cell lines defective of cohesion regulators DDX11 and ESCO2. The obtained synthetic lethality networks are strongly enriched for genes involved in DNA replication and mitosis and support the existence of parallel sister chromatid cohesion establishment pathways. Among the hits, we identify the chromatin binding, BRCT-domain containing protein PAXIP1 as a novel cohesin regulator. Depletion of PAXIP1 severely aggravates cohesion defects in ESCO2 mutant cells, leading to mitotic cell death. PAXIP1 promotes global chromatin association of cohesin, independent of DNA replication, a function that cannot be explained by indirect effects of PAXIP1 on transcription or DNA repair. Cohesin regulation by PAXIP1 requires its binding partner PAGR1 and a conserved FDF motif in PAGR1. PAXIP1 co-localizes with cohesin on multiple genomic loci, including active gene promoters and enhancers. Possibly, this newly identified role of PAXIP1-PAGR1 in regulating cohesin occupancy on chromatin is also relevant for previously described functions of PAXIP1 in transcription, immune cell maturation and DNA repair.
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Registered trials
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