دورية أكاديمية
Cyclin Kinase-independent role of p21 CDKN1A in the promotion of nascent DNA elongation in unstressed cells.
العنوان: | Cyclin Kinase-independent role of p21 CDKN1A in the promotion of nascent DNA elongation in unstressed cells. |
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المؤلفون: | Mansilla SF; Fundación Instituto Leloir-Instituto de Investigaciones Bioquímicas de Buenos Aires, Consejo de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina., Bertolin AP; Fundación Instituto Leloir-Instituto de Investigaciones Bioquímicas de Buenos Aires, Consejo de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina., Bergoglio V; Centre de Recherches en Cancérologie de Toulouse, Toulouse, France.; INSERM, Universite Paul Sabatier-CNRS, Université de Toulouse, Toulouse, France.; Laboratoire d'Excellence TOUCAN, Toulouse, France.; Equipe labellisée La Ligue contre le Cancer, Toulouse, France., Pillaire MJ; Centre de Recherches en Cancérologie de Toulouse, Toulouse, France.; INSERM, Universite Paul Sabatier-CNRS, Université de Toulouse, Toulouse, France.; Laboratoire d'Excellence TOUCAN, Toulouse, France.; Equipe labellisée La Ligue contre le Cancer, Toulouse, France., González Besteiro MA; Fundación Instituto Leloir-Instituto de Investigaciones Bioquímicas de Buenos Aires, Consejo de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina., Luzzani C; Laboratorio de Investigaciones Aplicadas en Neurociencias, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia, Belén de Escobar, Argentina., Miriuka SG; Laboratorio de Investigaciones Aplicadas en Neurociencias, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia, Belén de Escobar, Argentina., Cazaux C; Centre de Recherches en Cancérologie de Toulouse, Toulouse, France.; INSERM, Universite Paul Sabatier-CNRS, Université de Toulouse, Toulouse, France.; Laboratoire d'Excellence TOUCAN, Toulouse, France.; Equipe labellisée La Ligue contre le Cancer, Toulouse, France., Hoffmann JS; Centre de Recherches en Cancérologie de Toulouse, Toulouse, France.; INSERM, Universite Paul Sabatier-CNRS, Université de Toulouse, Toulouse, France.; Laboratoire d'Excellence TOUCAN, Toulouse, France.; Equipe labellisée La Ligue contre le Cancer, Toulouse, France., Gottifredi V; Fundación Instituto Leloir-Instituto de Investigaciones Bioquímicas de Buenos Aires, Consejo de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina. |
المصدر: | ELife [Elife] 2016 Oct 14; Vol. 5. Date of Electronic Publication: 2016 Oct 14. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012- |
مواضيع طبية MeSH: | Cell Division* , DNA Replication* , Genomic Instability*, Cyclin-Dependent Kinase Inhibitor p21/*metabolism , DNA/*biosynthesis, Cells, Cultured ; Humans |
مستخلص: | The levels of the cyclin-dependent kinase (CDK) inhibitor p21 are low in S phase and insufficient to inhibit CDKs. We show here that endogenous p21, instead of being residual, it is functional and necessary to preserve the genomic stability of unstressed cells. p21depletion slows down nascent DNA elongation, triggers permanent replication defects and promotes the instability of hard-to-replicate genomic regions, namely common fragile sites (CFS). The p21's PCNA interacting region (PIR), and not its CDK binding domain, is needed to prevent the replication defects and the genomic instability caused by p21 depletion. The alternative polymerase kappa is accountable for such defects as they were not observed after simultaneous depletion of both p21 and polymerase kappa. Hence, in CDK-independent manner, endogenous p21 prevents a type of genomic instability which is not triggered by endogenous DNA lesions but by a dysregulation in the DNA polymerase choice during genomic DNA synthesis. Competing Interests: The authors declare that no competing interests exist. |
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معلومات مُعتمدة: | R03 TW008924 United States TW FIC NIH HHS |
فهرسة مساهمة: | Keywords: DNA elongation; DNA replication; cancer biology; cell biology; common fragile site; genomic stability; human; p21 CDKN1A |
المشرفين على المادة: | 0 (CDKN1A protein, human) 0 (Cyclin-Dependent Kinase Inhibitor p21) 9007-49-2 (DNA) |
تواريخ الأحداث: | Date Created: 20161015 Date Completed: 20171024 Latest Revision: 20181113 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC5120883 |
DOI: | 10.7554/eLife.18020 |
PMID: | 27740454 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2050-084X |
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DOI: | 10.7554/eLife.18020 |