EXPERIMENT_TITLE: GSM7731255: HEL cells, LRCherry2.1-sgDCAF15#2, rep1; Homo sapiens; Hi-C
EXPERIMENT_DESIGN_LIBRARY_DESCRIPTOR_LIBRARY_CONSTRUCTION_PROTOC: Hi-C was performed on cells using the Arima High Coverage HiC Kit (Arima Genomics, A101030), following all manufacturer instructions Hi-C libraries were prepared using the NEBNext Ultra II DNA Library Prep Kit (New England BioLabs, E7645S) and NEBNext Dual Index Primers (New England BioLabs, E7600S), with modifications to the protocol as specified by the Arima High Coverage HiC Kit
STUDY_DESCRIPTOR_STUDY_ABSTRACT: The CRL4-DCAF15 E3 ubiquitin ligase complex is targeted by the aryl-sulfonamide molecular glues, leading to neo-substrate recruitment, ubiquitination, and proteasomal degradation. However, the physiological function of DCAF15 remains unknown. Using a domain-focused genetic screening approach, we reveal DCAF15 as an acute myeloid leukemia (AML)-biased dependency. Loss of DCAF15 results in suppression of AML through compromised replication fork integrity and consequent accumulation of DNA damage. Accordingly, DCAF15 loss sensitizes AML to replication stress-inducing therapeutics. Mechanistically, we discover that DCAF15 directly interacts with the SMC1A protein of the cohesin complex and destabilizes the cohesin regulatory factors PDS5A and CDCA5. Loss of PDS5A and CDCA5 removal precludes cohesin acetylation on chromatin, resulting in uncontrolled chromatin loop extrusion, defective DNA replication, and apoptosis. Collectively, our findings uncover an endogenous, cell autonomous function of DCAF15 in sustaining AML proliferation through post-translational control of cohesin dynamics. Overall design: HiC DNA-sequencing (HiC-seq) analysis in HEL human AML cell line without or with genetic knockout of DCAF15.
SAMPLE_TITLE: HEL cells, LRCherry2.1-sgDCAF15#2, rep1
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "source_name", "VALUE": "HEL"}, {"TAG": "cell line", "VALUE": "HEL"}, {"TAG": "cell type", "VALUE": "acute myeloid leukemia"}, {"TAG": "genotype", "VALUE": "DCAF15-KO"}, {"TAG": "geo_loc_name", "VALUE": "missing"}, {"TAG": "collection_date", "VALUE": "missing"}]
Pool_Member_@attributes_sample_title: HEL cells, LRCherry2.1-sgDCAF15#2, rep1
RUN_SET_RUN_Pool_Member_@attributes_sample_title: HEL cells, LRCherry2.1-sgDCAF15#2, rep1
RUN_SET_RUN_SRAFiles_SRAFile: [{"Alternatives": [null, null, null], "@attributes": {"cluster": "public", "filename": "SRR25749033.lite", "url": "https://sra-downloadb.be-md.ncbi.nlm.nih.gov/sos6/sra-pub-zq-40/SRR025/25749/SRR25749033/SRR25749033.lite.1", "size": "9211264353", "date": "2023-08-28 21:57:25", "md5": "f4e12baf1ba717ff2dc725697c1c3963", "version": "1", "semantic_name": "SRA Lite", "supertype": "Primary ETL", "sratoolkit": "1"}}, {"Alternatives": null, "@attributes": {"cluster": "public", "filename": "SRR25749033", "url": "https://sra-pub-run-odp.s3.amazonaws.com/sra/SRR25749033/SRR25749033", "size": "11712684353", "date": "2023-08-23 20:58:54", "md5": "67a1f69a602f7b569a860c39d01b9374", "version": "1", "semantic_name": "SRA Normalized", "supertype": "Primary ETL", "sratoolkit": "1"}}, {"Alternatives": null, "@attributes": {"cluster": "public", "filename": "DCAF15_1_S3_R2_001.fastq.gz", "size": "10559886404", "date": "2023-08-23 20:57:45", "md5": "ea475705a0edd0ae77dd727563af61b9", "version": "1", "semantic_name": "fastq", "supertype": "Original", "sratoolkit": "0"}}, {"Alternatives": null, "@attributes": {"cluster": "public", "filename": "DCAF15_1_S3_R1_001.fastq.gz", "size": "10253478728", "date": "2023-08-23 20:56:56", "md5": "b10fdc6798eaeed0cf7cc91a5530fc62", "version": "1", "semantic_name": "fastq", "supertype": "Original", "sratoolkit": "0"}}]