Mgs1 function at G-quadruplex structures during DNA replication
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MINI-REVIEW
Mgs1 function at G‑quadruplex structures during DNA replication Katrin Paeschke1 · Peter Burkovics2 Received: 25 September 2020 / Revised: 27 October 2020 / Accepted: 29 October 2020 © The Author(s) 2020
Abstract The coordinated action of DNA polymerases and DNA helicases is essential at genomic sites that are hard to replicate. Among these are sites that harbour G-quadruplex DNA structures (G4). G4s are stable alternative DNA structures, which have been implicated to be involved in important cellular processes like the regulation of gene expression or telomere maintenance. G4 structures were shown to hinder replication fork progression and cause genomic deletions, mutations and recombination events. Many helicases unwind G4 structures and preserve genome stability, but a detailed understanding of G4 replication and the re-start of stalled replication forks around formed G4 structures is not clear, yet. In our recent study, we identified that Mgs1 preferentially binds to G4 DNA structures in vitro and is associated with putative G4-forming chromosomal regions in vivo. Mgs1 binding to G4 motifs in vivo is partially dependent on the helicase Pif1. Pif1 is the major G4-unwinding helicase in S. cerevisiae. In the absence of Mgs1, we determined elevated gross chromosomal rearrangement (GCR) rates in yeast, similar to Pif1 deletion. Here, we highlight the recent findings and set these into context with a new mechanistic model. We propose that Mgs1’s functions support DNA replication at G4-forming regions. Keywords G-quadruplex · Replication · Mgs1 · Genome stability
Introduction Precise replication of the genome is essential for most eukaryotic cells, as it determines the fate of the daughter cells. Failure of precise replication can lead to genome instability, cancerous transformation or apoptosis. The continuous movement of the replication fork is often stalled by various obstacles, like different hard-to-replicate alterations on the template DNA strand, DNA-bound protein complexes, DNA damage or stable secondary structures (Aguilera and GarciaMuse 2013). The stalled replication fork can be rescued by Communicated by M. Kupiec. Katrin Paeschke and Peter Burkovics contributed equally to this work. * Katrin Paeschke kpaeschk@uni‑bonn.de * Peter Burkovics [email protected] 1
Department of Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany
Institute of Genetics, Biological Research Centre, Szeged, Hungary
2
different pathways, including a direct bypass of the lesion or template switching where the newly synthesised DNA strand serves as a template (Unk et al. 2010). Post-translational modifications of PCNA, a homotrimer ring-like protein, regulates the re-start/repair of the stalled fork (Moldovan et al. 2007; Arbel et al. 2020; Ripley et al. 2020). Ubiquitylation of PCNA by the Rad6/Rad18 complex activates the DNA damage tolerance pathway (Hoege et al. 2002) whereas PCNA SUMOylation inhibits unwanted recombination events at the stalled fork (Papouli et al. 2005; P
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