Review
Mechanisms of DNA damage repair in adult stem cells and implications for cancer formation

https://doi.org/10.1016/j.bbadis.2017.10.015Get rights and content
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Highlights

  • Stem cells must repair DNA damage to preserve genomic integrity and tissue homeostasis.

  • Epithelial tissue-specific stem cells have different DNA repair abilities.

  • Mutational processes associated with aberrant DNA repair are detected in cancer.

  • Targeting of DNA repair pathways constitutes a new approach to cancer therapy.

Abstract

Maintenance of genomic integrity in tissue-specific stem cells is critical for tissue homeostasis and the prevention of deleterious diseases such as cancer. Stem cells are subject to DNA damage induced by endogenous replication mishaps or exposure to exogenous agents. The type of DNA lesion and the cell cycle stage will invoke different DNA repair mechanisms depending on the intrinsic DNA repair machinery of a cell. Inappropriate DNA repair in stem cells can lead to cell death, or to the formation and accumulation of genetic alterations that can be transmitted to daughter cells and so is linked to cancer formation. DNA mutational signatures that are associated with DNA repair deficiencies or exposure to carcinogenic agents have been described in cancer. Here we review the most recent findings on DNA repair pathways activated in epithelial tissue stem and progenitor cells and their implications for cancer mutational signatures. We discuss how deep knowledge of early molecular events leading to carcinogenesis provides insights into DNA repair mechanisms operating in tumours and how these could be exploited therapeutically.

Keywords

DNA damage response
Cancer mutational signatures
Stem cells
Cell of origin of cancer

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