Dormant Origins as a Built-In Safeguard in Eukaryotic DNA Replication Against Genome Instability and Disease Development

DNA Repair (Amst). 2017 Aug;56:166-173. doi: 10.1016/j.dnarep.2017.06.019. Epub 2017 Jun 9.

Abstract

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.

Keywords: Cancer; Dormant replication origins; MCM2-7; Rare human genetic diseases; Replication stress; Replication-associated genome instability; Stem cells.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • DNA / metabolism
  • DNA Repair*
  • DNA Replication*
  • Eukaryota / genetics
  • Eukaryota / metabolism
  • Genomic Instability*
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Replication Origin*
  • Stem Cells / metabolism

Substances

  • DNA