Mms1 is an assistant for regulating G-quadruplex DNA structures

Schwindt, Eike; Paeschke, Katrin

doi:10.1007/s00294-017-0773-9

Cited by 11 publications

(11 citation statements)

References 56 publications

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“…We show that Mms1 is not required to maintain CEB1 stability at both leading-and lagging-CEB1 revealing that G4 structures targeted by Mms1 are not deleterious for CEB1 stability. Our results are in good agreement with previous observations showing that Mms1 supports Pif1 function at G4 motifs only on the lagging strand [22,37], whereas Pif1 is not required for CEB1 stabilisation [33]. Here we show that RPA recruits Pif1 to CEB1.…”

Section: Discussionsupporting

confidence: 93%

“…Alternatively, Pif1 could be directly recruited to G-rich motifs and G-quadruplex structures. Mms1 is a G4-DNA-binding protein that helps replication fork progression at G4 and Pif1 binding to specific G4 structures [22,37]. We show that Mms1 is not required to maintain CEB1 stability at both leading-and lagging-CEB1 revealing that G4 structures targeted by Mms1 are not deleterious for CEB1 stability.…”

Section: Discussionmentioning

confidence: 85%

“…Surprisingly, in pif1∆ cells CEB1 was unstable only when the G-quadruplexforming strand was the leading strand template [33]. This result is apparently counterintuitive since ssDNA is mostly formed during the discontinuous synthesis of the lagging strand DNA [35] and because Pif1 has been reported to act at the lagging strand [36] and binds G4 structures located in the lagging strand [22,37].…”

Section: Introductionmentioning

confidence: 99%

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RPA and Pif1 cooperate to remove G-rich structures at both leading and lagging strand

Maestroni¹,

Audry²,

Luciano³

et al. 2020

CST

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In Saccharomyces cerevisiae, the absence of Pif1 helicase induces the instability of G4-containing CEB1 minisatellite during leading strand but not lagging strand replication. We report that RPA and Pif1 cooperate to maintain CEB1 stability when the G4 forming strand is either on the leading or lagging strand templates. At the leading strand, RPA acts in the same pathway as Pif1 to maintain CEB1 stability. Consistent with this result, RPA coprecipitates with Pif1. This association between Pif1 and RPA is affected by the rfa1-D228Y mutation that lowers the affinity of RPA in particular for G-rich single-stranded DNA. At the lagging strand, in contrast to pif1∆, the rfa1-D228Y mutation strongly increases the frequency of CEB1 rearrangements. We explain that Pif1 is dispensable at the lagging strand DNA by the ability of RPA by itself to prevent formation of stable G-rich secondary structures during lagging strand synthesis. Remarkably, overexpression of Pif1 rescues the instability of CEB1 at the lagging strand in the rfa1-D228Y mutant indicating that Pif1 can also act at the lagging strand. We show that the effects of the rfa1-D228Y (rpa1-D223Y in fission yeast) are conserved in Schizosaccharomyces pombe. Finally, we report that RNase H1 interacts in a DNAdependent manner with RPA in budding yeast, however overexpression of RNase H1 does not rescue CEB1 instability observed in pif1∆ and rfa1-D228Y mutants. Collectively these results add new insights about the general role of RPA in preventing formation of DNA secondary structures and in coordinating the action of factors aimed at resolving them.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

RPA and Pif1 cooperate to remove G-rich structures at both leading and lagging strand

Maestroni¹,

Audry²,

Luciano³

et al. 2020

CST

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“…Considering that G4-containing promoters corresponded principally to high transcriptional levels in a genome-wide study (Hänsel-Hertsch et al, 2016), induction of transcription may be the main role of G4s at gene promoters. In addition, since, except for helicases and few other proteins (Budhathoki et al, 2015;Butovskaya et al, 2019;Chen et al, 2018;David et al, 2019;Gueddouda et al, 2017;Paramasivam et al, 2009;Sauer and Paeschke, 2017;Scalabrin et al, 2017b;Voter et al, 2018;Wu et al, 2019), the vast majority of G4 binding protein stabilizes G4s (Brázda et al, 2014;Schwindt and Paeschke, 2018;Tosoni et al, 2015), recruitment of transcription factors by G4-interacting proteins may be the most common mechanism.…”

Section: Discussionmentioning

confidence: 99%

Transcription factor recruitment by parallel G-quadruplexes to promote transcription: the case of herpes simplex virus-1 ICP4

Frasson

Soldà

Nadai

et al. 2020

Preprint

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G-quadruplexes (G4s), four-stranded nucleic acid structures that adopt several distinctive conformations, are abundant at gene promoters and have been proposed as transcription regulatory elements. G4s form in the herpes simplex virus-1 (HSV-1) genome during its viral cycle. Here by cross-linking/pull-down assay we identified ICP4 as the protein that most interacts with viral G4s during infection. In vitro and in infected cells, ICP4 specifically and directly bound and unfolded parallel G4s, including those present in HSV-1 immediate early gene promoters, and consequently induced transcription. This mechanism was also exploited by ICP4 to promote its own transcription. By proximity ligation assay we visualized ICP4 interaction at the single G4 in cells. G4 ligands inhibited ICP4 binding to G4s. Our results indicate the existence of a well-defined G4-viral protein network that regulates the productive HSV-1 cycle. They also point to G4s as elements that recruit transcription factors to activate transcription in cells.

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“…One possibility is that ToPif-mediated G4-resolving activity in vivo is regulated by an unidentified protein factor. It was recently reported that the proteins Mgs1 and Mms1 in S. cerevisiae binding to G4 motifs in vivo partially depends on the helicase ScPif1 (41,42). Although ScPif1 is the major G4-unwinding helicase in cells, in the absence of Mgs1, the gross chromosomal rearrangement (GCR) rates in yeast is increased, similar to Pif1 deletion (41).…”

Section: Mutational Analysis Of the Residues Involved In G4 Binding And Unfoldingmentioning

confidence: 99%

Structural mechanism underpinning Thermus oshimai Pif1-mediated G-quadruplex unfolding

Yang-Xue

Hai-Lei

Na-Nv

et al. 2021

Preprint

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G-quadruplexes (G4s) are unusual DNA structures and can stall DNA replication, causing genomic instability for the cell. Although the solved crystal structure of the DHX36 helicase demonstrated that G4 was specifically targeted by a DHX36-specific motif (DSM), lack of complete structural details for general G4-resolving helicases without specific target motifs remains a barrier to the complete understanding of the molecular basis underlying the recognition and unfolding of G4s. Herein, we present the first X-ray crystal structure of the Thermus oshimai Pif1 (ToPif) complexed with a G4, thereby mimicking the physiological G4 formed during DNA replication. Strictly different from the previous determined G4-helicase structure of DHX36, our structure revealed that ToPif1 recognizes the entire native G4 via a cluster of amino acids at domains 1B/2B constituting a G4-Recognizing Surface (GRS). The overall topology of the G4 structure solved in this work maintains its three-layered propeller-type G4 topology, with no significant reorganization of G-tetrads upon protein binding. The three G-tetrads in G4 were differentially recognized by GRS residues mainly through electrostatic, ionic interactions and hydrogen bonds formed between the GRS residues and the ribose-phosphate backbone. Our structure explains how helicases from distinct superfamilies adopt different strategies for recognizing and unfolding G4s.

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Mms1 is an assistant for regulating G-quadruplex DNA structures

Cited by 11 publications

References 56 publications

RPA and Pif1 cooperate to remove G-rich structures at both leading and lagging strand

RPA and Pif1 cooperate to remove G-rich structures at both leading and lagging strand

Transcription factor recruitment by parallel G-quadruplexes to promote transcription: the case of herpes simplex virus-1 ICP4

Structural mechanism underpinning Thermus oshimai Pif1-mediated G-quadruplex unfolding

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