Mgs1 protein supports genome stability via recognition of G‐quadruplex DNA structures

Abstract

The integrity of the genetic material is crucial for every organism. One intrinsic attack to genome stability is stalling of the replication fork which can result in DNA breakage. Several factors, such as DNA lesions or the formation of stable secondary structures (eg, G‐quadruplexes) can lead to replication fork stalling. G‐quadruplexes (G4s) are well‐characterized stable secondary DNA structures that can form within specific single‐stranded DNA sequence motifs and have been shown to block/pause the replication machinery. In most genomes several helicases have been described to regulate G4 unfolding to preserve genome integrity, however, different experiments raise the hypothesis that processing of G4s during DNA replication is more complex and requires additional, so far unknown, proteins. Here, we show that the Saccharomyces cerevisiae Mgs1 protein robustly binds to G4 structures in vitro and preferentially acts at regions with a strong potential to form G4 structures in vivo. Our results suggest that Mgs1 binds to G4‐forming sites and has a role in the maintenance of genome integrity.

Wrnip1 Prevents G4/R-Loop-Associated Genomic Instability

“…Consistently with data in yeast 34 , our PLA assay revealed a co-localization of WRNIP1 with G4structures at comparable levels in shWRNIP1 WT and shWRNIP1 T294A cells under unperturbed and . CC-BY-NC-ND 4.0 International license perpetuity.…”

“…The yeast homolog of WRNIP1, Mgs1 exhibits a high G4-binding affinity without requiring its ATPase activity 34 . Consistently with data in yeast, we reveal a co-localization of WRNIP1 to G4s upon MRS that does not require ATPase activity but is improved by loss of WRNIP1 UBZ domain.…”

Promoter G-quadruplexes and transcription factors cooperate to shape the cell type-specific transcriptome

“…G4s are dynamic structures that can be induced or unfolded upon interaction with G4-binding proteins [38][39][40][41] . We reasoned that the G4 landscape could be unique to each transcriptional program, hence cell type.…”

Az élesztő Mgs1 és a humán WRNIP1 fehérjék szerepe a G-kvadruplexet formáló DNS szakaszok replikációjában

“…Az Mgs1 fehérjének fontos szerepe van a replikációs villa zavartalan haladásában [137,160], így a genomstabilitás megőrzésében is [134], azonban a folyamat biokémiai mechanizmusa és a fehérje szerepének pontos funkciója még nem ismert. Németországi kollaborátorunk, Katrin Paeschke laboratóriumában élesztő egyhibrid kísérletben kimutatták, hogy az élesztő Mgs1 fehérje kötődik a G4-et tartalmazó régiókhoz [161]. Emellett ismert, hogy az Mgs1 fehérje humán homológja, a WRNIP1, kapcsolatban áll a G4 szekvenciák kicsavarására is képes WRN helikázzal [146].…”

“…4. Külföldi kollaborátoraink élesztő egyhibrid kísérletben, amelyben G4-kötő fehérjéket kerestek, az élesztő Mgs1-et pozitív találatként azonosították (ezt a kísérletet jelen dolgozat nem tartalmazza) [161].…”