دورية أكاديمية
أعرض في EDS

Impact of the interplay between stemness features, p53 and pol iota on replication pathway choices.

التفاصيل البيبلوغرافية
العنوان: Impact of the interplay between stemness features, p53 and pol iota on replication pathway choices.
المؤلفون: Ihle M; Department of Obstetrics and Gynecology, Ulm University, Ulm 89075, Germany., Biber S; Department of Obstetrics and Gynecology, Ulm University, Ulm 89075, Germany., Schroeder IS; Department of Biophysics, GSI Helmholtz Center for Heavy Ion Research, Darmstadt 64291, Germany., Blattner C; Institute for Biological and Chemical Systems - Biological Information Processing, Karlsruhe Institute of Technology, Karlsruhe 76021, Germany., Deniz M; Department of Obstetrics and Gynecology, Ulm University, Ulm 89075, Germany., Damia G; Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri-IRCCS Milan, Milan 20156, Italy., Gottifredi V; Cell cycle and Genomic Stability Laboratory, Fundación Instituto Leloir, Buenos Aires C1405BWE, Argentina., Wiesmüller L; Department of Obstetrics and Gynecology, Ulm University, Ulm 89075, Germany.
المصدر: Nucleic acids research [Nucleic Acids Res] 2021 Jul 21; Vol. 49 (13), pp. 7457-7475.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 1992- : Oxford : Oxford University Press
Original Publication: London, Information Retrieval ltd.
مواضيع طبية MeSH: DNA Replication*, DNA-Directed DNA Polymerase/*metabolism , Stem Cells/*metabolism , Tumor Suppressor Protein p53/*metabolism, Cell Differentiation/genetics ; Cells, Cultured ; DNA Helicases/metabolism ; Embryonic Stem Cells/metabolism ; Humans ; Neoplastic Stem Cells/metabolism ; Stress, Physiological/genetics ; DNA Polymerase iota
مستخلص: Using human embryonic, adult and cancer stem cells/stem cell-like cells (SCs), we demonstrate that DNA replication speed differs in SCs and their differentiated counterparts. While SCs decelerate DNA replication, differentiated cells synthesize DNA faster and accumulate DNA damage. Notably, both replication phenotypes depend on p53 and polymerase iota (POLι). By exploring protein interactions and newly synthesized DNA, we show that SCs promote complex formation of p53 and POLι at replication sites. Intriguingly, in SCs the translocase ZRANB3 is recruited to POLι and required for slow-down of DNA replication. The known role of ZRANB3 in fork reversal suggests that the p53-POLι complex mediates slow but safe bypass of replication barriers in SCs. In differentiated cells, POLι localizes more transiently to sites of DNA synthesis and no longer interacts with p53 facilitating fast POLι-dependent DNA replication. In this alternative scenario, POLι associates with the p53 target p21, which antagonizes PCNA poly-ubiquitination and, thereby potentially disfavors the recruitment of translocases. Altogether, we provide evidence for diametrically opposed DNA replication phenotypes in SCs and their differentiated counterparts putting DNA replication-based strategies in the spotlight for the creation of therapeutic opportunities targeting SCs.
(© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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المشرفين على المادة: 0 (TP53 protein, human)
0 (Tumor Suppressor Protein p53)
EC 2.7.7.7 (DNA-Directed DNA Polymerase)
EC 3.6.4.- (DNA Helicases)
EC 3.6.4.- (ZRANB3 protein, human)
EC 2.7.7.7 (DNA Polymerase iota)
EC 2.7.7.7 (POLI protein, human)
تواريخ الأحداث: Date Created: 20210624 Date Completed: 20210809 Latest Revision: 20221207
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC8287946
DOI: 10.1093/nar/gkab526
PMID: 34165573
قاعدة البيانات: MEDLINE
الوصف
تدمد:1362-4962
DOI:10.1093/nar/gkab526