دورية أكاديمية
Complementary CRISPR genome-wide genetic screens in PARP10-knockout and overexpressing cells identify synthetic interactions for PARP10-mediated cellular survival.
| العنوان: | Complementary CRISPR genome-wide genetic screens in PARP10-knockout and overexpressing cells identify synthetic interactions for PARP10-mediated cellular survival. |
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| المؤلفون: | Khatib JB; Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.; These authors contributed equally to this work., Schleicher EM; Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.; These authors contributed equally to this work., Jackson LM; Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA., Dhoonmoon A; Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA., Moldovan GL; Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA., Nicolae CM; Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. |
| المصدر: | Oncotarget [Oncotarget] 2022 Sep 28; Vol. 13, pp. 1078-1091. Date of Electronic Publication: 2022 Sep 28 (Print Publication: 2022). |
| نوع المنشور: | Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Impact Journals Country of Publication: United States NLM ID: 101532965 Publication Model: eCollection Cited Medium: Internet ISSN: 1949-2553 (Electronic) Linking ISSN: 19492553 NLM ISO Abbreviation: Oncotarget Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Albany, N.Y. : Impact Journals |
| مواضيع طبية MeSH: | Neoplasms*/genetics , Poly(ADP-ribose) Polymerases*/genetics , Poly(ADP-ribose) Polymerases*/metabolism, ADP Ribose Transferases/genetics ; Clustered Regularly Interspaced Short Palindromic Repeats ; DNA ; Humans ; Precision Medicine ; Proto-Oncogene Proteins/genetics |
| مستخلص: | PARP10 is a mono-ADP-ribosyltransferase with multiple cellular functions, including proliferation, apoptosis, metabolism and DNA repair. PARP10 is overexpressed in a significant proportion of tumors, particularly breast and ovarian cancers. Identifying genetic susceptibilities based on PARP10 expression levels is thus potentially relevant for finding new targets for precision oncology. Here, we performed a series of CRISPR genome-wide loss-of-function screens in isogenic control and PARP10-overexpressing or PARP10-knockout cell lines, to identify genetic determinants of PARP10-mediated cellular survival. We found that PARP10-overexpressing cells rely on multiple DNA repair genes for survival, including ATM, the master regulator of the DNA damage checkpoint. Moreover, we show that PARP10 impacts the recruitment of ATM to nascent DNA upon replication stress. Finally, we identify the CDK2-Cyclin E1 complex as essential for proliferation of PARP10-knockout cells. Our work identifies a network of functionally relevant PARP10 synthetic interactions, and reveals a set of factors which can potentially be targeted in personalized cancer therapy. Competing Interests: CONFLICTS OF INTEREST Authors have no conflicts of interest to declare. (Copyright: © 2022 Khatib et al.) |
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| معلومات مُعتمدة: | F31 CA243301 United States CA NCI NIH HHS; R01 CA244417 United States CA NCI NIH HHS; R01 ES026184 United States ES NIEHS NIH HHS |
| فهرسة مساهمة: | Keywords: ATM; CRISPR screens; PARP10; cancer cell proliferation; genome stability |
| المشرفين على المادة: | 0 (Proto-Oncogene Proteins) 9007-49-2 (DNA) EC 2.4.2.- (ADP Ribose Transferases) EC 2.4.2.30 (PARP10 protein, human) EC 2.4.2.30 (Poly(ADP-ribose) Polymerases) |
| تواريخ الأحداث: | Date Created: 20221003 Date Completed: 20221004 Latest Revision: 20221027 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC9518689 |
| DOI: | 10.18632/oncotarget.28277 |
| PMID: | 36187556 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1949-2553 |
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| DOI: | 10.18632/oncotarget.28277 |