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Maintenance of the ES Cell State

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The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
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Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
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In the CNS, neurogenesis, the birth of new neurons from stem cells, is limited to the hippocampus in adults. In other regions of the brain and spinal cord, neurogenesis is almost non-existent due to inhibitory influences from neuroglia, especially oligodendrocytes, and the absence of growth-stimulating cues. The myelin produced by oligodendrocytes in the CNS inhibits neuronal regeneration. Furthermore, astrocytes proliferate rapidly after neuronal damage, forming scar tissue that physically...
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Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
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In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells
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Maintaining genome stability in the nervous system.

Peter J McKinnon1

  • 1Department of Genetics, St. Jude Children's Research Hospital, Memphis Tennessee, USA.

Nature Neuroscience
|October 30, 2013
PubMed
Summary

Maintaining genome stability is crucial for nervous system development and function. DNA damage response pathways protect neural homeostasis, and their defects cause neurological disorders.

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Genome stability is essential for nervous system development and function.
  • Neurons require efficient DNA repair due to high replication during neurogenesis and long lifespan.
  • DNA damage response pathways are critical for maintaining neural homeostasis.

Purpose of the Study:

  • To highlight the importance of genome stability in the nervous system.
  • To explain the role of DNA damage response pathways in neural homeostasis.
  • To underscore the link between DNA damage signaling defects and neurological syndromes.

Main Methods:

  • Literature review on DNA damage response pathways in the nervous system.
  • Analysis of the impact of replication stress and DNA lesions on neural cells.

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  • Examination of human neurologic syndromes linked to compromised genome integrity.

    • Main Results:

    • Multiple DNA damage response pathways safeguard genetic fidelity during neurogenesis and in mature neurons.
    • Defects in DNA damage signaling lead to neurological syndromes with diverse neuropathology.
    • Genome integrity maintenance is vital for various neural functions.

    Conclusions:

    • Understanding DNA damage signaling is key to comprehending brain function.
    • Efficient cellular programs are necessary to protect the genome in the nervous system.
    • Compromised genome stability underlies various neurological disorders.