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DNA Replication Stress and Chromosomal Instability: Dangerous Liaisons
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Protective Mechanisms Against DNA Replication Stress in the Nervous System

Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil
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Genes 2020, 11(7), 730; https://doi.org/10.3390/genes11070730
Received: 27 May 2020 / Revised: 25 June 2020 / Accepted: 25 June 2020 / Published: 30 June 2020
(This article belongs to the Special Issue Protective Mechanisms Against DNA Replication Stress)
The precise replication of DNA and the successful segregation of chromosomes are essential for the faithful transmission of genetic information during the cell cycle. Alterations in the dynamics of genome replication, also referred to as DNA replication stress, may lead to DNA damage and, consequently, mutations and chromosomal rearrangements. Extensive research has revealed that DNA replication stress drives genome instability during tumorigenesis. Over decades, genetic studies of inherited syndromes have established a connection between the mutations in genes required for proper DNA repair/DNA damage responses and neurological diseases. It is becoming clear that both the prevention and the responses to replication stress are particularly important for nervous system development and function. The accurate regulation of cell proliferation is key for the expansion of progenitor pools during central nervous system (CNS) development, adult neurogenesis, and regeneration. Moreover, DNA replication stress in glial cells regulates CNS tumorigenesis and plays a role in neurodegenerative diseases such as ataxia telangiectasia (A-T). Here, we review how replication stress generation and replication stress response (RSR) contribute to the CNS development, homeostasis, and disease. Both cell-autonomous mechanisms, as well as the evidence of RSR-mediated alterations of the cellular microenvironment in the nervous system, were discussed. View Full-Text
Keywords: genome stability; neurologic disease; DNA damage; neurodevelopment; neurodegeneration; ATR; CNS; replication stress; DDR genome stability; neurologic disease; DNA damage; neurodevelopment; neurodegeneration; ATR; CNS; replication stress; DDR
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Forrer Charlier, C.; Martins, R.A.P. Protective Mechanisms Against DNA Replication Stress in the Nervous System. Genes 2020, 11, 730.

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