title: Biochemical mechanism of DSB end resection and its regulation.
abstract: DNA double-strand breaks (DSBs) in cells can undergo nucleolytic degradation to generate long 3' single-stranded DNA tails. This process is termed DNA end resection, and its occurrence effectively commits to break repair via homologous recombination, which entails the acquisition of genetic information from an intact, homologous donor DNA sequence. Recent advances, prompted by the identification of the nucleases that catalyze resection, have revealed intricate layers of functional redundancy, interconnectedness, and regulation. Here, we review the current state of the field with an emphasis on the major questions that remain to be answered. Topics addressed will include how resection initiates via the introduction of an endonucleolytic incision close to the break end, the molecular mechanism of the conserved MRE11 complex in conjunction with Sae2/CtIP within such a model, the role of BRCA1 and 53BP1 in regulating resection initiation in mammalian cells, the influence of chromatin in the resection process, and potential roles of novel factors.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: james.daley@yale.edu.
authors.forename: James M
authors.initials: JM
authors.lastname: Daley
authors.affiliation: Molecular and Cellular Biochemistry Department, Indiana University, Bloomington, IN 47405, USA.
authors.forename: Hengyao
authors.initials: H
authors.lastname: Niu
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Miller
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Sung
mesh_terms: D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D053904:DNA Breaks, Single-Stranded; D059766:DNA End-Joining Repair; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004706:Endodeoxyribonucleases; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D059765:Homologous Recombination; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000076228:MRE11 Homologue Protein; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D002352:Carrier Proteins; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C121766:MRE11 protein, human; D009687:Nuclear Proteins; C107849:SAE2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D004247:DNA; D004706:Endodeoxyribonucleases; D004720:Endonucleases; D000076228:MRE11 Homologue Protein; C410741:RBBP8 protein, human
keywords: Double-strand breaks; Helicases; Nucleases; Recombination; Resection