scholarly journals ATR Signaling Uncouples the Role of RAD51 Paralogs in Homologous Recombination and Replication Stress Response

Cell Reports ◽  
2019 ◽  
Vol 29 (3) ◽  
pp. 551-559.e4
Author(s):  
Sneha Saxena ◽  
Suruchi Dixit ◽  
Kumar Somyajit ◽  
Ganesh Nagaraju
Keyword(s):  
Stress Response ◽  
Homologous Recombination ◽  
Replication Stress ◽  
Rad51 Paralogs

scholarly journals The Role of the Rad55–Rad57 Complex in DNA Repair

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1390
Author(s):  
Upasana Roy ◽  
Eric C. Greene
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Repair ◽  
Homologous Recombination ◽  
Single Molecule ◽  
Genome Integrity ◽  
Genetic Studies ◽  
Biochemical Assays ◽  
Rad51 Paralogs ◽  
Higher Eukaryotes

Homologous recombination (HR) is a mechanism conserved from bacteria to humans essential for the accurate repair of DNA double-stranded breaks, and maintenance of genome integrity. In eukaryotes, the key DNA transactions in HR are catalyzed by the Rad51 recombinase, assisted by a host of regulatory factors including mediators such as Rad52 and Rad51 paralogs. Rad51 paralogs play a crucial role in regulating proper levels of HR, and mutations in the human counterparts have been associated with diseases such as cancer and Fanconi Anemia. In this review, we focus on the Saccharomyces cerevisiae Rad51 paralog complex Rad55–Rad57, which has served as a model for understanding the conserved role of Rad51 paralogs in higher eukaryotes. Here, we discuss the results from early genetic studies, biochemical assays, and new single-molecule observations that have together contributed to our current understanding of the molecular role of Rad55–Rad57 in HR.

scholarly journals Treacle and TOPBP1 control replication stress response in the nucleolus

2021 ◽  
Vol 220 (8) ◽  
Author(s):  
Artem K. Velichko ◽  
Natalia Ovsyannikova ◽  
Nadezhda V. Petrova ◽  
Artem V. Luzhin ◽  
Maria Vorobjeva ◽  
...  
Keyword(s):  
Stress Response ◽  
Genome Instability ◽  
Replication Stress ◽  
Low Complexity ◽  
Drug Induced ◽  
Response Factors ◽  
Checkpoint Activation ◽  
Stalled Replication Forks

Replication stress is one of the main sources of genome instability. Although the replication stress response in eukaryotic cells has been extensively studied, almost nothing is known about the replication stress response in nucleoli. Here, we demonstrate that initial replication stress–response factors, such as RPA, TOPBP1, and ATR, are recruited inside the nucleolus in response to drug-induced replication stress. The role of TOPBP1 goes beyond the typical replication stress response; it interacts with the low-complexity nucleolar protein Treacle (also referred to as TCOF1) and forms large Treacle–TOPBP1 foci inside the nucleolus. In response to replication stress, Treacle and TOPBP1 facilitate ATR signaling at stalled replication forks, reinforce ATR-mediated checkpoint activation inside the nucleolus, and promote the recruitment of downstream replication stress response proteins inside the nucleolus without forming nucleolar caps. Characterization of the Treacle–TOPBP1 interaction mode leads us to propose that these factors can form a molecular platform for efficient stress response in the nucleolus.

scholarly journals DNA Topoisomerase 3α Is Involved in Homologous Recombination Repair and Replication Stress Response in Trypanosoma cruzi

2021 ◽  
Vol 9 ◽  
Author(s):  
Héllida Marina Costa-Silva ◽  
Bruno Carvalho Resende ◽  
Adriana Castilhos Souza Umaki ◽  
Willian Prado ◽  
Marcelo Santos da Silva ◽  
...  
Keyword(s):  
Dna Damage ◽  
Stress Response ◽  
Cell Growth ◽  
Homologous Recombination ◽  
Trypanosoma Cruzi ◽  
Gamma Radiation ◽  
Replication Stress ◽  
Homologous Recombination Repair ◽  
Dormant Cells ◽  
Recombination Repair

DNA topoisomerases are enzymes that modulate DNA topology. Among them, topoisomerase 3α is engaged in genomic maintenance acting in DNA replication termination, sister chromatid separation, and dissolution of recombination intermediates. To evaluate the role of this enzyme in Trypanosoma cruzi, the etiologic agent of Chagas disease, a topoisomerase 3α knockout parasite (TcTopo3α KO) was generated, and the parasite growth, as well as its response to several DNA damage agents, were evaluated. There was no growth alteration caused by the TcTopo3α knockout in epimastigote forms, but a higher dormancy rate was observed. TcTopo3α KO trypomastigote forms displayed reduced invasion rates in LLC-MK2 cells when compared with the wild-type lineage. Amastigote proliferation was also compromised in the TcTopo3α KO, and a higher number of dormant cells was observed. Additionally, TcTopo3α KO epimastigotes were not able to recover cell growth after gamma radiation exposure, suggesting the involvement of topoisomerase 3α in homologous recombination. These parasites were also sensitive to drugs that generate replication stress, such as cisplatin (Cis), hydroxyurea (HU), and methyl methanesulfonate (MMS). In response to HU and Cis treatments, TcTopo3α KO parasites showed a slower cell growth and was not able to efficiently repair the DNA damage induced by these genotoxic agents. The cell growth phenotype observed after MMS treatment was similar to that observed after gamma radiation, although there were fewer dormant cells after MMS exposure. TcTopo3α KO parasites showed a population with sub-G1 DNA content and strong γH2A signal 48 h after MMS treatment. So, it is possible that DNA-damaged cell proliferation due to the absence of TcTopo3α leads to cell death. Whole genome sequencing of MMS-treated parasites showed a significant reduction in the content of the multigene families DFG-1 and RHS, and also a possible erosion of the sub-telomeric region from chromosome 22, relative to non-treated knockout parasites. Southern blot experiments suggest telomere shortening, which could indicate genomic instability in TcTopo3α KO cells owing to MMS treatment. Thus, topoisomerase 3α is important for homologous recombination repair and replication stress in T. cruzi, even though all the pathways in which this enzyme participates during the replication stress response remains elusive.

scholarly journals Role of a Candida albicans Nrm1/Whi5 homologue in cell cycle gene expression and DNA replication stress response

2012 ◽  
Vol 84 (4) ◽  
pp. 778-794 ◽  
Author(s):  
Ayala Ofir ◽  
Kay Hofmann ◽  
Esther Weindling ◽  
Tsvia Gildor ◽  
Katherine S. Barker ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Candida Albicans ◽  
Dna Replication ◽  
Stress Response ◽  
Replication Stress ◽  
Cell Cycle Gene ◽  
Dna Replication Stress ◽  
Cell Cycle Gene Expression

scholarly journals Mrc1-Dependent Chromatin Compaction Represses DNA Double-Stranded Break Repair by Homologous Recombination Upon Replication Stress

2021 ◽  
Vol 9 ◽  
Author(s):  
Poyuan Xing ◽  
Yang Dong ◽  
Jingyu Zhao ◽  
Zhou Zhou ◽  
Zhao Li ◽  
...  
Keyword(s):  
Dna Replication ◽  
Homologous Recombination ◽  
Critical Role ◽  
Protein A ◽  
Replication Stress ◽  
Dependent Manner ◽  
Dsb Repair ◽  
Chromatin Compaction ◽  
End Resection

The coordination of DNA replication and repair is critical for the maintenance of genome stability. It has been shown that the Mrc1-mediated S phase checkpoint inhibits DNA double-stranded break (DSB) repair through homologous recombination (HR). How the replication checkpoint inhibits HR remains only partially understood. Here we show that replication stress induces the suppression of both Sgs1/Dna2- and Exo1-mediated resection pathways in an Mrc1-dependent manner. As a result, the loading of the single-stranded DNA binding factor replication protein A (RPA) and Rad51 and DSB repair by HR were severely impaired under replication stress. Notably, the deletion of MRC1 partially restored the recruitment of resection enzymes, DSB end resection, and the loading of RPA and Rad51. The role of Mrc1 in inhibiting DSB end resection is independent of Csm3, Tof1, or Ctf4. Mechanistically, we reveal that replication stress induces global chromatin compaction in a manner partially dependent on Mrc1, and this chromatin compaction limits the access of chromatin remodeling factors and HR proteins, leading to the suppression of HR. Our study reveals a critical role of the Mrc1-dependent chromatin structure change in coordinating DNA replication and recombination under replication stress.

scholarly journals The Role of the Human Psoralen 4 (hPso4) Protein Complex in Replication Stress and Homologous Recombination

2014 ◽  
Vol 289 (20) ◽  
pp. 14009-14019 ◽  
Author(s):  
Mohammad Abbas ◽  
Ilanchezhian Shanmugam ◽  
Manal Bsaili ◽  
Robert Hromas ◽  
Monte Shaheen
Keyword(s):  
Homologous Recombination ◽  
Protein Complex ◽  
Replication Stress

Analysis of replication profiles reveals key role of RFC-Ctf18 in yeast replication stress response

2010 ◽  
Vol 17 (11) ◽  
pp. 1391-1397 ◽  
Author(s):  
Laure Crabbé ◽  
Aubin Thomas ◽  
Véronique Pantesco ◽  
John De Vos ◽  
Philippe Pasero ◽  
...  
Keyword(s):  
Stress Response ◽  
Replication Stress

scholarly journals Constitutive role of the Fanconi anemia D2 gene in the replication stress response

2017 ◽  
Vol 292 (49) ◽  
pp. 20184-20195 ◽  
Author(s):  
Yanyan Tian ◽  
Xi Shen ◽  
Rui Wang ◽  
Naeh L. Klages-Mundt ◽  
Erica J. Lynn ◽  
...  
Keyword(s):  
Stress Response ◽  
Fanconi Anemia ◽  
Replication Stress
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