Making the best of the loose ends: Mre11/Rad50 complexes and Sae2 promote DNA double-strand break resection.
Double-strand breaks in chromosomal DNA are repaired efficiently in eukaryotic cells through pathways that involve direct religation of broken ends, or through pathways that utilize an unbroken, homologous DNA molecule as a template for replication. Pathways of repair that require homology initiate with the resection of the 5' strand at the break site, to uncover the 3' single-stranded DNA that becomes a critical intermediate in single-strand annealing and in homologous strand exchange. Resection of the 5' strand is regulated to occur most efficiently in S and G(2) phases of the cell cycle when sister chromatids are present as recombination templates. The mechanisms governing resection in eukaryotes have been elusive for many years, but recent work has identified the major players in short-range processing of DNA ends as well as the extensive resection of breaks that has been observed in vivo. This review focuses on the Mre11/Rad50/Xrs2(Nbs1) complex and the Sae2(CtIP) protein and their roles in initiating both short-range and long-range resection, the effects of topoisomerase-DNA conjugates on resection in vivo, and the relationship between these factors and NHEJ proteins in regulating 5' strand resection in eukaryotic cells.
The Howard Hughes Medical Institute, The Department of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, TX 78712, USA. tpaull@mail.utexas.edu
Tanya T
TT
Paull
D017766:Acid Anhydride Hydrolases; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D026942:DNA Topoisomerases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000076228:MRE11 Homologue Protein; D046912:Multiprotein Complexes / Q000378:metabolism*; D011995:Recombination, Genetic / Q000235:genetics / Q000502:physiology*; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism*
D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D046912:Multiprotein Complexes; C470301:UBA2 protein, human; D000076228:MRE11 Homologue Protein; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D026942:DNA Topoisomerases; D044764:Ubiquitin-Activating Enzymes; D045643:DNA Repair Enzymes