title: The Mre11/Rad50/Nbs1 complex functions in resection-based DNA end joining in Xenopus laevis.
abstract: 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.
authors.affiliation: Divisions of Medicine and Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Bailrigg, Lancaster LA1 4YQ, UK.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Taylor
authors.forename: Sophie M
authors.initials: SM
authors.lastname: Cecillon
authors.forename: Antonio
authors.initials: A
authors.lastname: Bonis
authors.forename: J Ross
authors.initials: JR
authors.lastname: Chapman
authors.forename: Lawrence F
authors.initials: LF
authors.lastname: Povirk
authors.forename: Howard D
authors.initials: HD
authors.lastname: Lindsay
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D045643:DNA Repair Enzymes; D051747:DNA-Activated Protein Kinase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000072200:Ku Autoantigen; D000076228:MRE11 Homologue Protein; D010063:Ovum / Q000378:metabolism; D011995:Recombination, Genetic; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D029867:Xenopus Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D034961:Antigens, Nuclear; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C510917:Mre11 protein, Xenopus; C511600:NBN protein, Xenopus; C542167:Rad50 protein, Xenopus; D025521:Tumor Suppressor Proteins; D029867:Xenopus Proteins; D051747:DNA-Activated Protein Kinase; D000076228:MRE11 Homologue Protein; D000072200:Ku Autoantigen; D045643:DNA Repair Enzymes