The Mre11/Rad50/Nbs1 complex functions in resection-based DNA end joining in Xenopus laevis. 2010

Elaine M Taylor, and Sophie M Cecillon, and Antonio Bonis, and J Ross Chapman, and Lawrence F Povirk, and Howard D Lindsay
Divisions of Medicine and Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Bailrigg, Lancaster LA1 4YQ, UK.

The repair of DNA double-strand breaks (DSBs) is essential to maintain genomic integrity. In higher eukaryotes, DNA DSBs are predominantly repaired by non-homologous end joining (NHEJ), but DNA ends can also be joined by an alternative error-prone mechanism termed microhomology-mediated end joining (MMEJ). In MMEJ, the repair of DNA breaks is mediated by annealing at regions of microhomology and is always associated with deletions at the break site. In budding yeast, the Mre11/Rad5/Xrs2 complex has been demonstrated to play a role in both classical NHEJ and MMEJ, but the involvement of the analogous MRE11/RAD50/NBS1 (MRN) complex in end joining in higher eukaryotes is less certain. Here we demonstrate that in Xenopus laevis egg extracts, the MRN complex is not required for classical DNA-PK-dependent NHEJ. However, the XMRN complex is necessary for resection-based end joining of mismatched DNA ends. This XMRN-dependent end joining process is independent of the core NHEJ components Ku70 and DNA-PK, occurs with delayed kinetics relative to classical NHEJ and brings about repair at sites of microhomology. These data indicate a role for the X. laevis MRN complex in MMEJ.

UI MeSH Term Description Entries
D010063 Ovum A mature haploid female germ cell extruded from the OVARY at OVULATION. Egg,Egg, Unfertilized,Ova,Eggs, Unfertilized,Unfertilized Egg,Unfertilized Eggs
D011995 Recombination, Genetic Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses. Genetic Recombination,Recombination,Genetic Recombinations,Recombinations,Recombinations, Genetic
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D000072200 Ku Autoantigen An ATP-dependent DNA HELICASE that preferentially binds SINGLE-STRANDED DNA. It is a heterodimer consisting of an 80 kDa subunit (XRCC5) and 70 kDa subunit (XRCC6) that functions with DNA LIGASE IV in the repair of DOUBLE-STRANDED DNA BREAKS and V(D)J RECOMBINATION. G22P1 Antigen,Ku Antigen,Ku Autoantigen, 70 kDa,Ku Autoantigen, 80 kDa,Ku Heterodimer,Ku Protein,Ku70 Antigen,Ku80 Antigen,X-ray Repair Cross-Complementing Protein 5,X-ray Repair Cross-Complementing Protein 6,XRCC5 Protein,XRCC6 Protein,Antigen, G22P1,Antigen, Ku,Antigen, Ku70,Antigen, Ku80,Autoantigen, Ku,Heterodimer, Ku,X ray Repair Cross Complementing Protein 5,X ray Repair Cross Complementing Protein 6
D000076228 MRE11 Homologue Protein A component of the MRN complex along with Rad50 and Nibrin. Together, these perform a critical function in the repair of DOUBLE-STRANDED DNA BREAKS; RECOMBINATIONAL DNA REPAIR; maintenance of TELOMERE integrity and MEIOSIS. MRE11, which contains a poly(ADP)-ribose binding motif and associates with PARP1, possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity. Mutations in the MRE11 gene are associated with ATAXIA-TELANGIECTASIA-like disorder 1. MRE11A Protein,Meiotic Recombination 11 Homolog 1 Protein,Homologue Protein, MRE11
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014982 Xenopus laevis The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals. Platanna,X. laevis,Platannas,X. laevi
D045643 DNA Repair Enzymes Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions. DNA Repair Enzyme,Enzyme, DNA Repair,Enzymes, DNA Repair,Repair Enzyme, DNA,Repair Enzymes, DNA

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