DNA Repair in Stem Cell Maintenance and Conversion to Cancer Stem Cells

  • S. L. Gerson
  • J. Reese
  • J. Kenyon
Conference paper
Part of the Springer Series on Biofilms book series (SCHERING FOUND, volume 2006/5)


Genomic stability is essential for cell and organism longevity. Without genomic stability, replication errors and external stress as well as direct forms of DNA damage can induce mutations, which decrease cell survival, cause altered gene expression, and can lead to cellular transformation. All represent the antithesis of maintenance of normal stem cell function. We argue here that genomic stability is essential for stem cell maintenance and longevity. This concept is supported by human diseases associated with premature aging and animal models of DNA damage repair abnormalities all of which lead to abnormalities of stem cell survival. Furthermore, with competitive repopulation, hematopoietic stem cell survival can be assessed in the face of DNA repair defects, and results from these studies support the general conclusion that chemotherapy and other forms of DNA damage lead to stem cell failure syndromes and malignant transformation most commonly along the myeloid and lymphoid pathways. Thus one origin of the cancer stem cell phenotype is the inability to maintain genomic stability among the stem cell population leading to mutational alterations and transformation. Capturing stem cells at this transition point represents an exciting field of discovery possibly leading to early detection and therapeutic interventions.


Stem Cell Mismatch Repair Nucleotide Excision Repair Microsatellite Instability Premature Aging 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Supported in part by grants from the National Institutes of Health, 5P30-CA-043703 and 5R01-AG-024916, and the State of Ohio Third Frontier Program.


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Case Comprehensive Cancer Center Division of Hematology/OncologyCase Western Reserve UniversityIreland Cancer Center, University Hospitals Case Medical CenterClevelandUSA

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