Mechanisms of DNA damage repair in adult stem cells and implications for cancer formation
Details
Publication Year 2018-01, Volume 1864, Issue #1, Page 89-101
Journal Title
Biochim Biophys Acta
Publication Type
Journal Article
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.
Publisher
Elsevier
Keywords
Adult Stem Cells/*physiology; Animals; Carcinogenesis/*genetics/pathology; DNA Damage/genetics; DNA Repair/*physiology; Humans; Neoplastic Stem Cells/*pathology/physiology
WEHI Research Division(s)
Molecular Medicine
PubMed ID
29038050
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2017-11-16 04:56:15
Last Modified: 2018-05-31 09:15:18
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