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

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

A meiotic XPF-ERCC1-like complex recognizes joint molecule recombination intermediates to promote crossover formation

De Muyt, Arnaud ; Pyatnitskaya, Alexandra ; Andréani, Jessica ; Ranjha, Lepakshi ; Laureau, Raphaëlle ; Fernandez-Vega, Ambra ; Holoch, Daniel ; Girard, Elodie ; Govin, Jérome ; Margueron, Raphaël ; Couté, Yohann ; Cejka, Petr ; Guérois, Raphaël ; Borde, Valérie

In: Genes and development, 2018, vol. 32, no. 3-4, p. 283-296

Meiotic crossover formation requires the stabilization of early recombination intermediates by a set of proteins and occurs within the environment of the chromosome axis, a structure important for the regulation of meiotic recombination events. The molecular mechanisms underlying and connecting crossover recombination and axis localization are elusive. Here, we identified the ZZS...