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Università della Svizzera italiana

Crossover or non-crossover outcomes : tailored processing of homologous recombination intermediates

Sanchez, Aurore ; Reginato, Giordano ; Cejka, Petr

In: Current opinion in genetics & development, 2021, vol. 71, p. 39-47

DNA breaks may arise accidentally in vegetative cells or in a programmed manner in meiosis. The usage of a DNA template makes homologous recombination potentially error-free, however, recombination is not always accurate. Cells possess a remarkable capacity to tailor processing of recombination intermediates to fulfill a particular need. Vegetatively growing cells aim to maintain genome...

Università della Svizzera italiana

The MRE11 complex : a versatile toolkit for the repair of broken DNA

Reginato, Giordano ; Cejka, Petr

In: DNA repair, 2020, vol. 91–92, no. July–August, p. 13 p

When DNA breaks, the ends need to be stabilized and processed to facilitate subsequent repair, which can occur by either direct but error-prone end-joining with another broken DNA molecule or a more accurate homology-directed repair by the recombination machinery. At the same time, the presence of broken DNA triggers a signaling cascade that regulates the repair events and cellular progression...

Università della Svizzera italiana

SAMHD1 promotes DNA end resection to facilitate DNA repair by homologous recombination

Daddacha, Waaqo ; Koyen, Allyson E. ; Bastien, Amanda J. ; Head,Pamela Sara E. ; Dhere, Vishal R. ; Nabeta, Geraldine N. ; Connolly, Erin C. ; Werner, Erica ; Madden, Matthew Z. ; Daly, Michele B. ; Minten, Elizabeth V. ; Whelan, Donna R. ; Schlafstein, Ashley J. ; Zhang, Hui ; Anand, Roopesh ; Doronio, Christine ; Withers, Allison E. ; Shepard, Caitlin ; Sundaram, Ranjini K. ; Deng, Xingming ; Dynan, William S. ; Wang, Ya ; Bindra, Ranjit S. ; Cejka, Petr ; Rothenberg, Eli ; Doetsch, Paul W. ; Kim, Baek ; Yu, David S.

In: Cell reports, 2017, vol. 20, no. 8, p. 1921-1935

DNA double-strand break (DSB) repair by homologous recombination (HR) is initiated by CtIP/MRN-mediated DNA end resection to maintain genome integrity. SAMHD1 is a dNTP triphosphohydrolase, which restricts HIV- 1 infection, and mutations are associated with Aicardi-Goutières syndrome and cancer. We show that SAMHD1 has a dNTPase-independent function in promoting DNA end resection to facilitate...

Università della Svizzera italiana

Main steps in DNA double-strand break repair : An introduction to homologous recombination and related processes

Ranjha, Lepakshi ; Howard, Sean Michael ; Cejka, Petr

In: Chromosoma, 2018, vol. 127, no. 2 (June), p. 187–214

DNA double-strand breaks arise accidentally upon exposure of DNA to radiation, chemicals or result from faulty DNA metabolic processes. DNA breaks can also be introduced in a programmed manner, such as during the maturation of the immune system, meiosis or cancer chemo- or radiotherapy. Cells have developed a variety of repair pathways, which are fine-tuned to the specific needs of a cell....

Università della Svizzera italiana

Regulatory control of DNA end resection by Sae2 phosphorylation

Cannavo, Elda ; Johnson, Dominic ; Andres, Sara N. ; Kissling, Vera M. ; Reinert, Julia K. ; Garcia, Valerie ; Erie, Dorothy A. ; Hess, Daniel ; Thomä, Nicolas H. ; Enchev, Radoslav I. ; Peter, Matthias ; Williams, R. Scott ; Neale, Matt J. ; Cejka, Petr

In: Nature communications, 2018, vol. 9, p. 4016

DNA end resection plays a critical function in DNA double-strand break repair pathway choice. Resected DNA ends are refractory to end-joining mechanisms and are instead channeled to homology-directed repair. Using biochemical, genetic, and imaging methods, we show that phosphorylation of Saccharomyces cerevisiae Sae2 controls its capacity to promote the Mre11-Rad50-Xrs2 (MRX) nuclease to...

Università della Svizzera italiana

NBS1 promotes the endonuclease of the MRE11-RAD50 complex by sensing CtIP phosphorylation

Anand, Roopesh ; Jasrotia, Arti ; Bundschuh, Diana ; Howard, Sean Michael ; Ranjha, Lepakshi ; Stucki, Manuel ; Cejka, Petr

In: The EMBO Journal, 2019, vol. 38, no. 7, p. e101005

DNA end resection initiates DNA break repair by homologous recombination. MRE11-RAD50-NBS1 and phosphorylated CtIP perform the first resection step by MRE11-catalyzed endonucleolytic DNA cleavage. Human NBS1, more than its Xrs2 homologue from Saccharomyces cerevisiae, is crucial for this process, highlighting complex mechanisms that regulate the MRE11 nuclease in high eukaryotes. Using a...

Università della Svizzera italiana

Stepwise 5' DNA end-specific resection of DNA breaks by the Mre11-Rad50-Xrs2 and Sae2 nuclease ensemble

Cannavo, Elda ; Reginato, Giordano ; Cejka, Petr

In: Proceedings of the national academy of sciences of the United States of America, 2019, vol. 116, no. 12 (March 19), p. 5505-5513

To repair DNA double-strand breaks by homologous recombination, the 5′-terminated DNA strands must first be resected to produce 3′ overhangs. Mre11 from Saccharomyces cerevisiae is a 3′ → 5′ exonuclease that is responsible for 5′ end degradation in vivo. Using plasmid-length DNA substrates and purified recombinant proteins, we show that the combined exonuclease and endonuclease...

Università della Svizzera italiana

Physiological protein blocks direct the Mre11–Rad50–Xrs2 and Sae2 nuclease complex to initiate DNA end resection

Reginato, Giordano ; Cannavo, Elda ; Cejka, Petr

In: Genes and Development, 2017, vol. 31, no. 23-24, p. 2325-2330

DNA double-strand break repair by homologous recombination is initiated by DNA end resection, which is commenced by the Mre11–Rad50–Xrs2 complex and Sae2 in yeast. Here we report that the nonhomologous end joining factor Ku limits the exonuclease activity of Mre11 and promotes its endonuclease to cleave 5'-terminated DNA strands at break sites. Following initial endonucleolytic cleavage...

Université de Fribourg

An armadillo-domain protein participates in a telomerase interaction network

Dokládal, Ladislav ; Benková, Eva ; Honys, David ; Dup?áková, Nikoleta ; Lee, Lan-Ying ; Gelvin, Stanton B. ; Sýkorová, Eva

In: Plant Molecular Biology, 2018, vol. 97, no. 4, p. 407–420

Key messageArabidopsis and human ARM protein interact with telomerase. Deregulated mRNA levels of DNA repair and ribosomal protein genes in an Arabidopsis arm mutant suggest non-telomeric ARM function. The human homolog ARMC6 interacts with hTRF2.AbstractTelomerase maintains telomeres and has proposed non-telomeric functions. We previously identified interaction of the C- terminal domain of...