Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double strand break ends
By Zhu Zhu, W. Chung, E. Shim, Sang Eun Lee, G. Ira. Cell, 2008
1,107 citations recorded by the source corpus.
Summary Formation of single-strand DNA (ssDNA) tails at a double-strand break (DSB) is a key step in homologous recombination and DNA damage signaling. The enzyme(s) producing ssDNA at DSBs in eukaryotes remains unknown. We monitored 5’-strand resection at inducible DSB ends and identified proteins required for two stages of resection: initiation and long-range 5’-strand resection. The Mre11-Rad50-Xrs2 complex (MRX) initiates 5’ degradation, whereas Sgs1 and Dna2 degrade 5’-strands exposing long 3’-strands at 4.4 kb/h rate. Deletion of SGS1 or DNA2 reduces resection and DSB repair by single strand annealing between distant repeats. Resection in the absence of SGS1 or DNA2 depends on Exo1. In exo1Δ sgs1Δ mutants the MRX complex and Sae2 in a stepwise manner generate only few hundred nucleotides of ssDNA at the break resulting in inefficient gene conversion and G2/M damage checkpoint arrest. We provide the first comprehensive model of the early steps of DSB repair in eukaryotes.
Subfields: Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/542f11bec5149c7ba482b01c6e421d6804024c63
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Citations in the corpus
- Regulation of homologous recombination in eukaryotes (2010, background): “Extended resection is achieved by the 5 → 3 exonuclease activity of Exo1 or the helicase activity of Sgs1 in cooperation with the endonuclease activity of Dna2 (103, 173).”
- BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair. (2011, background): “In the physical absence of MRX, resection is kinetically delayed (Mimitou and Symington 2008; Zhu et al. 2008), whereas in the nuclease-deficient strain, there is no delay (Llorente and Symington 2004).”
- Sources of DNA double-strand breaks and models of recombinational DNA repair. (2014, neutral): “…IP ( fo ld in cr ea se ) 12 10 8 6 4 2 0 0 1 2 3 4 5 6 (ii) (iii) (iv) (v) (vi) (vii) Strand invasion Primer extension Rad51 loading p2 p3 p5 p5 p4 p1 A B C D 0 1 3 5 8 Cite this article as Cold Spring Harb Perspect Biol 2014;6:a016428 7 2008; Zhu et al. 2008; Cejka et al. 2010; Niu et al. 2010).”
- Repair of strand breaks by homologous recombination. (2013, background): “More extensive resection involves the 50-30 exonuclease Exo1 or the combined helicase/nuclease activities of Sgs1/Dna2 (Mimitou and Symington 2008; Zhu et al. 2008).”