BIOMAT Database Logo BIOMAT Database Logo

The MRX complex regulates Exo1 resection activity by altering DNA end structure. 2018

Elisa Gobbini, and Corinne Cassani, and Jacopo Vertemara, and Weibin Wang, and Fabiana Mambretti, and Erika Casari, and Patrick Sung, and Renata Tisi, and Giuseppe Zampella, and Maria Pia Longhese
Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy.

Homologous recombination is triggered by nucleolytic degradation (resection) of DNA double-strand breaks (DSBs). DSB resection requires the Mre11-Rad50-Xrs2 (MRX) complex, which promotes the activity of Exo1 nuclease through a poorly understood mechanism. Here, we describe the Mre11-R10T mutant variant that accelerates DSB resection compared to wild-type Mre11 by potentiating Exo1-mediated processing. This increased Exo1 resection activity leads to a decreased association of the Ku complex to DSBs and an enhanced DSB resection in G1, indicating that Exo1 has a direct function in preventing Ku association with DSBs. Molecular dynamics simulations show that rotation of the Mre11 capping domains is able to induce unwinding of double-strand DNA (dsDNA). The R10T substitution causes altered orientation of the Mre11 capping domain that leads to persistent melting of the dsDNA end. We propose that MRX creates a specific DNA end structure that promotes Exo1 resection activity by facilitating the persistence of this nuclease on the DSB ends, uncovering a novel MRX function in DSB resection.

UI MeSH Term Description Entries
D004271 DNA, Fungal Deoxyribonucleic acid that makes up the genetic material of fungi. Fungal DNA
D004706 Endodeoxyribonucleases A group of enzymes catalyzing the endonucleolytic cleavage of DNA. They include members of EC 3.1.21.-, EC 3.1.22.-, EC 3.1.23.- (DNA RESTRICTION ENZYMES), EC 3.1.24.- (DNA RESTRICTION ENZYMES), and EC 3.1.25.-.
D005090 Exodeoxyribonucleases A family of enzymes that catalyze the exonucleolytic cleavage of DNA. It includes members of the class EC 3.1.11 that produce 5'-phosphomonoesters as cleavage products. DNA Exonucleases,Exonucleases, DNA
D000072417 Protein Domains Discrete protein structural units that may fold independently of the rest of the protein and have their own functions. Peptide Domain,Protein Domain,Domain, Peptide,Domain, Protein,Domains, Peptide,Domains, Protein,Peptide Domains
D012441 Saccharomyces cerevisiae A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement. Baker's Yeast,Brewer's Yeast,Candida robusta,S. cerevisiae,Saccharomyces capensis,Saccharomyces italicus,Saccharomyces oviformis,Saccharomyces uvarum var. melibiosus,Yeast, Baker's,Yeast, Brewer's,Baker Yeast,S cerevisiae,Baker's Yeasts,Yeast, Baker
D046912 Multiprotein Complexes Macromolecular complexes formed from the association of defined protein subunits. Macromolecular Protein Complexes,Complexes, Macromolecular Protein,Complexes, Multiprotein,Protein Complexes, Macromolecular
D053903 DNA Breaks, Double-Stranded Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently. Double-Stranded DNA Breaks,Double-Strand DNA Breaks,Double-Stranded DNA Break,Break, Double-Strand DNA,Break, Double-Stranded DNA,Breaks, Double-Strand DNA,Breaks, Double-Stranded DNA,DNA Break, Double-Strand,DNA Break, Double-Stranded,DNA Breaks, Double Stranded,DNA Breaks, Double-Strand,Double Strand DNA Breaks,Double Stranded DNA Break,Double Stranded DNA Breaks,Double-Strand DNA Break
D029701 Saccharomyces cerevisiae Proteins Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes. Baker's Yeast Proteins,S cerevisiae Proteins

Related Publications

Elisa Gobbini, and Corinne Cassani, and Jacopo Vertemara, and Weibin Wang, and Fabiana Mambretti, and Erika Casari, and Patrick Sung, and Renata Tisi, and Giuseppe Zampella, and Maria Pia Longhese
Local unwinding of double-strand DNA ends by the MRX complex promotes Exo1 processing activity.
January 2018, Molecular & cellular oncology,
Elisa Gobbini, and Corinne Cassani, and Jacopo Vertemara, and Weibin Wang, and Fabiana Mambretti, and Erika Casari, and Patrick Sung, and Renata Tisi, and Giuseppe Zampella, and Maria Pia Longhese
PCNA promotes processive DNA end resection by Exo1.
November 2013, Nucleic acids research,
Elisa Gobbini, and Corinne Cassani, and Jacopo Vertemara, and Weibin Wang, and Fabiana Mambretti, and Erika Casari, and Patrick Sung, and Renata Tisi, and Giuseppe Zampella, and Maria Pia Longhese
The SOSS1 single-stranded DNA binding complex promotes DNA end resection in concert with Exo1.
January 2013, The EMBO journal,
Elisa Gobbini, and Corinne Cassani, and Jacopo Vertemara, and Weibin Wang, and Fabiana Mambretti, and Erika Casari, and Patrick Sung, and Renata Tisi, and Giuseppe Zampella, and Maria Pia Longhese
Phosphorylation of EXO1 by CDKs 1 and 2 regulates DNA end resection and repair pathway choice.
April 2014, Nature communications,
Elisa Gobbini, and Corinne Cassani, and Jacopo Vertemara, and Weibin Wang, and Fabiana Mambretti, and Erika Casari, and Patrick Sung, and Renata Tisi, and Giuseppe Zampella, and Maria Pia Longhese
Ku prevents Exo1 and Sgs1-dependent resection of DNA ends in the absence of a functional MRX complex or Sae2.
October 2010, The EMBO journal,
Elisa Gobbini, and Corinne Cassani, and Jacopo Vertemara, and Weibin Wang, and Fabiana Mambretti, and Erika Casari, and Patrick Sung, and Renata Tisi, and Giuseppe Zampella, and Maria Pia Longhese
The chromatin remodeler Chd1 supports MRX and Exo1 functions in resection of DNA double-strand breaks.
September 2021, PLoS genetics,
Elisa Gobbini, and Corinne Cassani, and Jacopo Vertemara, and Weibin Wang, and Fabiana Mambretti, and Erika Casari, and Patrick Sung, and Renata Tisi, and Giuseppe Zampella, and Maria Pia Longhese
ZGRF1 promotes end resection of DNA homologous recombination via forming complex with BRCA1/EXO1.
September 2021, Cell death discovery,
Elisa Gobbini, and Corinne Cassani, and Jacopo Vertemara, and Weibin Wang, and Fabiana Mambretti, and Erika Casari, and Patrick Sung, and Renata Tisi, and Giuseppe Zampella, and Maria Pia Longhese
Phospho-dependent recruitment of the yeast NuA4 acetyltransferase complex by MRX at DNA breaks regulates RPA dynamics during resection.
October 2018, Proceedings of the National Academy of Sciences of the United States of America,
Elisa Gobbini, and Corinne Cassani, and Jacopo Vertemara, and Weibin Wang, and Fabiana Mambretti, and Erika Casari, and Patrick Sung, and Renata Tisi, and Giuseppe Zampella, and Maria Pia Longhese
The BRCA1-RAP80 complex regulates DNA repair mechanism utilization by restricting end resection.
April 2011, The Journal of biological chemistry,
Elisa Gobbini, and Corinne Cassani, and Jacopo Vertemara, and Weibin Wang, and Fabiana Mambretti, and Erika Casari, and Patrick Sung, and Renata Tisi, and Giuseppe Zampella, and Maria Pia Longhese
Correction to: ZGRF1 promotes end resection of DNA homologous recombination via forming complex with BRCA1/EXO1.
November 2022, Cell death discovery,
Copied contents to your clipboard!