دورية أكاديمية
أعرض في EDS

Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair.

التفاصيل البيبلوغرافية
العنوان: Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair.
المؤلفون: Wienert B; Innovative Genomics Institute, University of California, Berkeley, CA, 94703, USA.; Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94703, USA.; Gladstone Institutes, San Francisco, CA, 94158, USA., Nguyen DN; Department of Microbiology and Immunology, University of California, San Francisco, CA, 94143, USA.; Diabetes Center, University of California, San Francisco, CA, 94143, USA.; Department of Medicine, University of California, San Francisco, CA, 94143, USA., Guenther A; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, 93106, USA., Feng SJ; Innovative Genomics Institute, University of California, Berkeley, CA, 94703, USA.; Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94703, USA., Locke MN; Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94703, USA., Wyman SK; Innovative Genomics Institute, University of California, Berkeley, CA, 94703, USA., Shin J; Department of Biology, Institute of Molecular Health Sciences, ETH Zürich, 8093, Zurich, Switzerland., Kazane KR; Innovative Genomics Institute, University of California, Berkeley, CA, 94703, USA.; Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94703, USA., Gregory GL; Gladstone Institutes, San Francisco, CA, 94158, USA., Carter MAM; Gladstone Institutes, San Francisco, CA, 94158, USA., Wright F; Department of Microbiology and Immunology, University of California, San Francisco, CA, 94143, USA., Conklin BR; Gladstone Institutes, San Francisco, CA, 94158, USA.; Departments of Medicine, Ophthalmology, and Pharmacology, University of California, San Francisco, CA, 94143, USA., Marson A; Innovative Genomics Institute, University of California, Berkeley, CA, 94703, USA.; Department of Microbiology and Immunology, University of California, San Francisco, CA, 94143, USA.; Diabetes Center, University of California, San Francisco, CA, 94143, USA.; Department of Medicine, University of California, San Francisco, CA, 94143, USA.; Parker Institute for Cancer Immunotherapy, San Francisco, CA, 94129, USA.; Chan Zuckerberg Biohub, San Francisco, CA, 94158, USA., Richardson CD; Innovative Genomics Institute, University of California, Berkeley, CA, 94703, USA. chris.richardson@lifesci.ucsb.edu.; Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94703, USA. chris.richardson@lifesci.ucsb.edu.; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, 93106, USA. chris.richardson@lifesci.ucsb.edu., Corn JE; Innovative Genomics Institute, University of California, Berkeley, CA, 94703, USA. jacob.corn@biol.ethz.ch.; Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94703, USA. jacob.corn@biol.ethz.ch.; Department of Biology, Institute of Molecular Health Sciences, ETH Zürich, 8093, Zurich, Switzerland. jacob.corn@biol.ethz.ch.
المصدر: Nature communications [Nat Commun] 2020 Apr 30; Vol. 11 (1), pp. 2109. Date of Electronic Publication: 2020 Apr 30.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: CRISPR-Cas Systems* , Recombinational DNA Repair*, Cell Cycle Proteins/*antagonists & inhibitors , Cell Cycle Proteins/*genetics , Protein Serine-Threonine Kinases/*antagonists & inhibitors , Protein Serine-Threonine Kinases/*genetics, DNA Breaks, Double-Stranded ; Gene Editing ; Genetic Engineering/methods ; HCT116 Cells ; HEK293 Cells ; HeLa Cells ; Homologous Recombination ; Humans ; K562 Cells ; Phenotype ; RNA, Guide, CRISPR-Cas Systems/metabolism ; S Phase
مستخلص: Repair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification via homology directed repair (HDR) from donor DNA. Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away from other repair outcomes. Here, we utilize a pooled CRISPR screen to define host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor). We find that the Fanconi Anemia (FA) pathway is required for dsDonor HDR and that other genes act to repress HDR. Small molecule inhibition of one of these repressors, CDC7, by XL413 and other inhibitors increases the efficiency of HDR by up to 3.5 fold in many contexts, including primary T cells. XL413 stimulates HDR during a reversible slowing of S-phase that is unexplored for Cas9-induced HDR. We anticipate that XL413 and other such rationally developed inhibitors will be useful tools for gene modification.
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معلومات مُعتمدة: DP2 HL141006 United States HL NHLBI NIH HHS; L40 AI140341 United States AI NIAID NIH HHS; P30 AI027763 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (Cell Cycle Proteins)
0 (RNA, Guide, CRISPR-Cas Systems)
EC 2.7.1.- (CDC7 protein, human)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
تواريخ الأحداث: Date Created: 20200502 Date Completed: 20200807 Latest Revision: 20240425
رمز التحديث: 20240425
مُعرف محوري في PubMed: PMC7193628
DOI: 10.1038/s41467-020-15845-1
PMID: 32355159
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-020-15845-1