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

Abstract

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.

Working on Genomic Stability: From the S-Phase to Mitosis

“…One important feature for successful replication is the tight control of origin licensing. Replication origin licensing takes place from late mitosis until the end of G1 by loading double MCM2-7 hexamers at origins and is a highly CDK activity-dependent process (Table 1) [20][21][22]; for a recent review on origin licensing see [23]. In this way, at the beginning of the S-phase, MCM hexamers are activated at hundreds of thousands of origins distributed in a non-random way throughout the genome forming the ring of the replicative helicase that unwinds the DNA ahead of DNA polymerase [20,[24][25][26].…”

A Survey of Essential Genome Stability Genes Reveals That Replication Stress Mitigation Is Critical for Peri-Implantation Embryogenesis

“…Cyclin dependent kinase activity promotes E2F transactivation to initiate replication at the G1/S transition (Kent and Leone, 2019). Replication then proceeds throughout the S-phase with origins firing in temporal coordination and DNA synthesis occurring across the entirety of the genome (Burgers and Kunkel, 2017;Limas and Cook, 2019). Intrinsic and extrinsic factors may disrupt replication fork processivity: a phenomenon known as "replication stress" (Zeman and Cimprich, 2014).…”

Bacterial quorum sensing signal arrests phytoplankton cell division and protects against virus-induced mortality

“…Moreover, significant increases in relative transcript abundances of DNA replication fork machinery (i.e., DNA polymerases α, ε, and δ, DNA primase, replication protein A, topoisomerases (TOPO), the minichromosomal maintenance complex, proliferating cell nuclear antigen, and replication factor C, Fig. 4; Dataset S1) at 72 h post HHQ exposure, suggests an intent to replicate DNA, a hallmark of S-phase 33 . However, despite this observed induction of DNA replication machinery, cell cycle analysis demonstrated DNA synthesis was severely diminished following HHQ exposure (Fig.…”