Rtt105 functions as a chaperone for replication protein A to preserve genome stability

Li, Shuqi; Xu, Zongbin; Xu, Jiawei; Zuo, Linyu; Yu, Cheng-Rong; Pu, Zheng; Gan, Haiyun; Wang, Xuezheng; Li, Longtu; Sharma, Sushma; Chabes, Andrei; Li, Di; Wang, Sheng; Zheng, Shu-Jian; Li, Jinbao; Chen, Xuefeng; Sun, Yujie; Xu, Dongyi; Han, Junhong; Chan, Kui Ming; Qiao, Zhi; Feng, Jianxun; Li, Qing

doi:10.15252/embj.201899154

Cited by 25 publications

(54 citation statements)

References 89 publications

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“…We report that Pif1 associates with RPA and that this association is affected in the rfa1-D228Y mutant and by DNA digestion, suggesting that Pif1-RPA association relies on specific DNA structures. In addition we show that rtt105∆ mutation, which decreases the level of RPA associated with ssDNA (as the rfa1-D228Y mutation) [44,45], strongly affects CEB1 stability at both leading and lagging strands. These results reveal the importance of Rtt105 in promoting the replication of G4-forming CEB1 minisatellite, during leading strand and lagging strand synthesis, and confirm that the level of RPA is crucial for CEB1 stability.…”

Section: Discussionmentioning

confidence: 79%

“…Rtt105 functions as an RPA chaperone that escorts RPA to the nucleus and facilitates RPA loading onto ssDNA [44]. Consequently, RTT105 inactivation reduces the association of RPA with ssDNA generated during DNA transactions and affects multiple RPA functions [44,45]. We examined the importance of Rtt105 on the stability of the leading-CEB1 and lagging-CEB1.…”

Section: Rtt105 Is Required To Stabilize Both the Leading-ceb1 And Lamentioning

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: Discussionmentioning

confidence: 79%

Section: Rtt105 Is Required To Stabilize Both the Leading-ceb1 And Lamentioning

confidence: 99%

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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“…Although RPA has a high affinity for ssDNA in vitro , its loading on ssDNA in the complex cellular environment may rely on additional cofactor(s). A recent study describes how RPA is loaded on ssDNA regions in budding yeast ( 39 ). It was also demonstrated that RPA loading on ssDNA is also assisted by Cdc45, an essential component of the replicative DNA helicase ( 40 ).…”

Section: Modes Of Ssdna Binding: Rpa Loading Diffusion and Dissociationmentioning

confidence: 99%

Replication protein A: a multifunctional protein with roles in DNA replication, repair and beyond

Dueva

Iliakis

2020

NAR Cancer

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Single-stranded DNA (ssDNA) forms continuously during DNA replication and is an important intermediate during recombination-mediated repair of damaged DNA. Replication protein A (RPA) is the major eukaryotic ssDNA-binding protein. As such, RPA protects the transiently formed ssDNA from nucleolytic degradation and serves as a physical platform for the recruitment of DNA damage response factors. Prominent and well-studied RPA-interacting partners are the tumor suppressor protein p53, the RAD51 recombinase and the ATR-interacting proteins ATRIP and ETAA1. RPA interactions are also documented with the helicases BLM, WRN and SMARCAL1/HARP, as well as the nucleotide excision repair proteins XPA, XPG and XPF–ERCC1. Besides its well-studied roles in DNA replication (restart) and repair, accumulating evidence shows that RPA is engaged in DNA activities in a broader biological context, including nucleosome assembly on nascent chromatin, regulation of gene expression, telomere maintenance and numerous other aspects of nucleic acid metabolism. In addition, novel RPA inhibitors show promising effects in cancer treatment, as single agents or in combination with chemotherapeutics. Since the biochemical properties of RPA and its roles in DNA repair have been extensively reviewed, here we focus on recent discoveries describing several non-canonical functions.

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“…Six OB-folds in the different subunits contribute to the ssDNA-binding ability of RPA. Recently, we found that, in budding yeast, the previously uncharacterized protein Rtt105 functions as an RPA chaperone to facilitate RPA entry into the nucleus and to promote the deposition of RPA onto ssDNA [128,129]. Cells lacking Rtt105 present a dramatic genome instability phenotype.…”

Section: Rpa: a Platform For Histone Chaperone Coordinationmentioning

confidence: 99%

“…Cells lacking Rtt105 present a dramatic genome instability phenotype. Remarkably, Rtt105 promotes a fast and stretching mode of RPA binding to ssDNA, suggesting that regulation of the RPA-ssDNA binding platform is crucial for DNA replication [128,129]. In addition to binding ssDNA, RPA also participates in the regulation of DNA replication.…”

Section: Rpa: a Platform For Histone Chaperone Coordinationmentioning

confidence: 99%

The replisome guides nucleosome assembly during DNA replication

Zhang

Feng

2020

Cell Biosci

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Nucleosome assembly during DNA replication is tightly coupled to ongoing DNA synthesis. This process, termed DNA replication-coupled (RC) nucleosome assembly, is essential for chromatin replication and has a great impact on both genome stability maintenance and epigenetic inheritance. This review discusses a set of recent findings regarding the role of replisome components contributing to RC nucleosome assembly. Starting with a brief introduction to the factors involved in nucleosome assembly and some aspects of the architecture of the eukaryotic replisome, we discuss studies from yeast to mammalian cells and the interactions of replisome components with histones and histone chaperones. We describe the proposed functions of replisome components during RC nucleosome assembly and discuss their impacts on histone segregation and implications for epigenetic inheritance.

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Rtt105 functions as a chaperone for replication protein A to preserve genome stability

Cited by 25 publications

References 89 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

Replication protein A: a multifunctional protein with roles in DNA replication, repair and beyond

The replisome guides nucleosome assembly during DNA replication

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