Essential Function of Dicer in Resolving DNA Damage in the Rapidly Dividing Cells of the Developing and Malignant Cerebellum.

Autor:	Swahari V; Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: swahari@email.unc.edu., Nakamura A; Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA; Neurobiology Curriculum, University of North Carolina, Chapel Hill, NC 27599, USA., Baran-Gale J; Curriculum in Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA., Garcia I; Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Neurology, University of North Carolina, Chapel Hill, NC 27599, USA., Crowther AJ; Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Neurology, University of North Carolina, Chapel Hill, NC 27599, USA., Sons R; Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA., Gershon TR; Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA; Neurobiology Curriculum, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Neurology, University of North Carolina, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA., Hammond S; Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA., Sethupathy P; Curriculum in Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA., Deshmukh M; Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA; Neurobiology Curriculum, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: mohanish@med.unc.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2016 Jan 12; Vol. 14 (2), pp. 216-24. Date of Electronic Publication: 2015 Dec 31.
DOI:	10.1016/j.celrep.2015.12.037
Abstrakt:	Maintenance of genomic integrity is critical during neurodevelopment, particularly in rapidly dividing cerebellar granule neuronal precursors that experience constitutive replication-associated DNA damage. As Dicer was recently recognized to have an unexpected function in the DNA damage response, we examined whether Dicer was important for preserving genomic integrity in the developing brain. We report that deletion of Dicer in the developing mouse cerebellum resulted in the accumulation of DNA damage leading to cerebellar progenitor degeneration, which was rescued with p53 deficiency; deletion of DGCR8 also resulted in similar DNA damage and cerebellar degeneration. Dicer deficiency also resulted in DNA damage and death in other rapidly dividing cells including embryonic stem cells and the malignant cerebellar progenitors in a mouse model of medulloblastoma. Together, these results identify an essential function of Dicer in resolving the spontaneous DNA damage that occurs during the rapid proliferation of developmental progenitors and malignant cells. (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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