DNA damage responses in murine Pre-B cells with genetic deficiencies in damage response genes.

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We compare the transcriptional programs activated in response to genotoxic DNA damage induced by ionizing radiation (IR) in abl pre-B cells from mice deficient in DNA damage response (DDR) genes Atm, Mre11, Mdc1, H2ax, 53bp1, and DNA-PKcs. We identified a core IR-specific transcriptional response that occurs in abl pre-B cells from WT mice and compared the response of the other genotypes to the WT response. We also identified genotype specific responses and compared those to each other. The WT response includes many processes involved in lymphocyte development and immune response, as well as responses associated with the molecular mechanisms of cancer, such as TP53 signaling. As expected, there is a range of similarity in transcriptional profiles in comparison to WT cells, with Atm-/- cells being the most different from the core WT DDR and Mre11 hypomorph (Mre11A/A) cells also very dissimilar to WT and other genotypes. For example, NF-kB-related signaling and CD40 signaling are deficient in both Atm-/- and Mre11A/A cells, but present in all other genotypes. In contrast, IR-induced TP53 signaling is seen in the Mre11A/A cells, while these responses are not seen in the Atm-/- cells. By examining the similarities and differences in the signaling pathways in response to IR when specific genes are absent, our results further illustrate the contribution of each gene to the DDR. The microarray gene expression data discussed in this paper have been deposited in NCBI's Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/) and are accessible under accession number GSE116388.", "claims": [{"id": "claim-data-access", "statement": "The microarray gene expression data discussed in this paper have been deposited in NCBI’s Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/) and are accessible under accession number GSE116388.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31757180", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The microarray gene expression data discussed in this paper have been deposited in NCBI’s Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/) and are accessible under accession number GSE116388."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified a core IR-specific transcriptional response in WT abl pre-B cells and characterized genotype-specific differences, with Atm-/- cells most different from the core WT DDR and Mre11A/A cells also very dissimilar to WT and other genotypes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:31757180", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We identified a core IR-specific transcriptional response that occurs in abl pre-B cells from WT mice and compared the response of the other genotypes to the WT response."}, {"asset": "source:pmid:31757180", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "As expected, there is a range of similarity in transcriptional profiles in comparison to WT cells, with Atm-/- cells being the most different from the core WT DDR and Mre11 hypomorph (Mre11A/A) cells also very dissimilar to WT and other genotypes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified a core IR-specific transcriptional response in WT abl pre-B cells and characterized genotype-specific differences, with Atm-/- cells most different from the core WT DDR and Mre11A/A cells also very dissimilar to WT and other genotypes.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:31757180"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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