DYNLL1 binds to MRE11 to limit DNA end resection in BRCA1-deficient cells

Limited DNA end resection is the key to impaired homologous recombination in BRCA1 -mutant cancer cells. Here, using a loss-of-function CRISPR screen, we identify DYNLL1 as an inhibitor of DNA end resection. The loss of DYNLL1 enables DNA end resection and restores homologous recombination in BRCA1...

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Veröffentlicht in:	Nature (London) Jg. 563; H. 7732; S. 522 - 526
Hauptverfasser:	He, Yizhou Joseph, Meghani, Khyati, Caron, Marie-Christine, Yang, Chunyu, Ronato, Daryl A., Bian, Jie, Sharma, Anchal, Moore, Jessica, Niraj, Joshi, Detappe, Alexandre, Doench, John G., Legube, Gaelle, Root, David E., D’Andrea, Alan D., Drané, Pascal, De, Subhajyoti, Konstantinopoulos, Panagiotis A., Masson, Jean-Yves, Chowdhury, Dipanjan
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 01.11.2018 Nature Publishing Group
Schlagworte:	13/1 13/106 13/109 13/89 14/19 14/63 38/77 631/337/1427/2190 631/67/1059/2326 Adenosine diphosphate Biochemistry, Molecular Biology Biotechnology BRCA genes BRCA1 protein BRCA1 Protein - deficiency BRCA1 Protein - genetics Breast cancer Cancer Cancer cells Cancer genetics Cancer therapies Cell Line, Tumor Chemotherapy Chromosome Aberrations Chromosome abnormalities CRISPR CRISPR-Cas Systems - genetics Cytoplasmic Dyneins - metabolism Deoxyribonucleic acid DNA DNA - metabolism DNA damage DNA Damage - drug effects DNA helicase DNA methylation DNA repair Drug resistance Drug Resistance, Neoplasm - drug effects Drugs Endonuclease FDA approval Female Gene Editing Gene expression Genes Genes, BRCA1 Genetic research Genomes Genomic Instability - drug effects Homologous recombination Homologous Recombination - drug effects Homology Humanities and Social Sciences Humans Ionizing radiation Lesions Life Sciences Molecular biology Monosaccharides MRE11 Homologue Protein - metabolism MRE11 protein multidisciplinary Mutation Nucleases Ovarian cancer Ovarian carcinoma Ovarian Neoplasms - genetics Ovarian Neoplasms - pathology Platinum Platinum - pharmacology Poly(ADP-ribose) Poly(ADP-ribose) polymerase Poly(ADP-ribose) Polymerase Inhibitors - pharmacology Protein Binding Proteins Recombinational DNA Repair - drug effects Ribose Science Science (multidisciplinary) Surgery Transcription Factors - metabolism Somatic Structural Variants Homologous Recombination-mediated Repair BRCA Mutant Cells Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) High-grade Serous Ovarian Carcinoma (HGSOC)
ISSN:	0028-0836, 1476-4687, 1476-4687
Online-Zugang:	Volltext
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