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

Clare E. Weeden, Marie-Liesse Labat

Research output: Contribution to journalReview article

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)89-101
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1864
Issue number1
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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