Preparation for DNA replication: the key to a successful S phase

• Published in: FEBS letters Vol. 593; no. 20; pp. 2853 - 2867
• Main Authors: Limas, Juanita C., Cook, Jeanette Gowen
• Format: Journal Article
• Language: English
• Published: England 01-10-2019
• Subjects: Animals; Carcinogenesis - genetics; Carcinogenesis - metabolism; Carcinogenesis - pathology; cell cycle; Cell Cycle - genetics; Cell Cycle Checkpoints - genetics; checkpoint; Cyclin-Dependent Kinases - genetics; Cyclin-Dependent Kinases - metabolism; DNA Replication; Eukaryotic Cells - cytology; Eukaryotic Cells - metabolism; G1 Phase - genetics; Gene Expression Regulation; Genome; genome stability; Genomic Instability; Humans; origin licensing; replication stress; S Phase - genetics; Signal Transduction; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; checkpoint; origin licensing; genome stability; DNA replication; replication stress; cell cycle
• ISSN: 0014-5793; 1873-3468; 1873-3468
• DOI: 10.1002/1873-3468.13619

Successful genome duplication is required for cell proliferation and demands extraordinary precision and accuracy. The mechanisms by which cells enter, progress through, and exit S phase are intense areas of focus in the cell cycle and genome stability fields. Key molecular events in the G1 phase of the cell division cycle, especially origin licensing, are essential for pre‐establishing conditions for efficient DNA replication during the subsequent S phase. If G1 events are poorly regulated or disordered, then DNA replication can be compromised leading to genome instability, a hallmark of tumorigenesis. Upon entry into S phase, coordinated origin firing and replication progression ensure complete, timely, and precise chromosome replication. Both G1 and S phase progressions are controlled by master cell cycle protein kinases and ubiquitin ligases that govern the activity and abundance of DNA replication factors. In this short review, we describe current understanding and recent developments related to G1 progression and S phase entrance and exit with a particular focus on origin licensing regulation in vertebrates.