DNA replication is a prerequisite for cell proliferation, yet it can be increasingly challenging for a eukaryotic cell to faithfully duplicate its genome as its size and complexity expands. Dormant origins now emerge as a key component for cells to successfully accomplish such a demanding but essential task. In this perspective, we will first provide an overview of the fundamental processes eukaryotic cells have developed to regulate origin licensing and firing. With a special focus on mammalian systems, we will then highlight the role of dormant origins in preventing replication-associated genome instability and their functional interplay with proteins involved in the DNA damage repair response for tumor suppression. Lastly, deficiencies in the origin licensing machinery will be discussed in relation to their influence on stem cell maintenance and human diseases.
Bibliographical noteFunding Information:
We thank Dr. Alex Sobeck for critical comments and suggestions. The authors were supported in part by a grant from the National Cancer Institute (CA187290).
© 2017 Elsevier B.V.
Copyright 2017 Elsevier B.V., All rights reserved.
- Dormant replication origins
- Rare human genetic diseases
- Replication stress
- Replication-associated genome instability
- Stem cells