Replication Licensing Aberrations, Replication Stress, and Genomic Instability

Michalis Petropoulos; Spyridon Champeris Tsaniras; Stavros Taraviras; Zoi Lygerou

doi:10.1016/j.tibs.2019.03.011

Replication Licensing Aberrations, Replication Stress, and Genomic Instability

Trends Biochem Sci. 2019 Sep;44(9):752-764. doi: 10.1016/j.tibs.2019.03.011. Epub 2019 May 1.

Authors

Michalis Petropoulos¹, Spyridon Champeris Tsaniras², Stavros Taraviras³, Zoi Lygerou⁴

Affiliations

¹ Department of Biology, School of Medicine, University of Patras, Patras 26504, Greece.
² Department of Physiology, School of Medicine, University of Patras, Patras 26504, Greece.
³ Department of Physiology, School of Medicine, University of Patras, Patras 26504, Greece. Electronic address: taraviras@med.upatras.gr.
⁴ Department of Biology, School of Medicine, University of Patras, Patras 26504, Greece. Electronic address: lygerou@med.upatras.gr.

PMID: 31054805
DOI: 10.1016/j.tibs.2019.03.011

Abstract

Strict regulation of DNA replication is of fundamental significance for the maintenance of genome stability. Licensing of origins of DNA replication is a critical event for timely genome duplication. Errors in replication licensing control lead to genomic instability across evolution. Here, we present accumulating evidence that aberrant replication licensing is linked to oncogene-induced replication stress and poses a major threat to genome stability, promoting tumorigenesis. Oncogene activation can lead to defects in where along the genome and when during the cell cycle licensing takes place, resulting in replication stress. We also discuss the potential of replication licensing as a specific target for novel anticancer therapies.

Keywords: CDC6; CDT1; MCM; ORC; oncogenes; replication fork stalling; replication origins; tumorigenesis.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

DNA / genetics*
DNA Replication*
Genomic Instability / genetics*
Humans
Stress, Physiological / genetics*

Substances

DNA