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The SWI/SNF ATP-dependent nucleosome remodeler promotes resection initiation at a DNA double-strand break in yeast.
Nucleic Acids Res. 2017 Jun 02; 45(10):5887-5900.NA

Abstract

DNA double-strand breaks (DSBs) are repaired by either the non-homologous end joining (NHEJ) or homologous recombination (HR) pathway. Pathway choice is determined by the generation of 3΄ single-strand DNA overhangs at the break that are initiated by the action of the Mre11-Rad50-Xrs2 (MRX) complex to direct repair toward HR. DSB repair occurs in the context of chromatin, and multiple chromatin regulators have been shown to play important roles in the repair process. We have investigated the role of the SWI/SNF ATP-dependent nucleosome-remodeling complex in the repair of a defined DNA DSB. SWI/SNF was previously shown to regulate presynaptic events in HR, but its function in these events is unknown. We find that in the absence of functional SWI/SNF, the initiation of DNA end resection is significantly delayed. The delay in resection initiation is accompanied by impaired recruitment of MRX to the DSB, and other functions of MRX in HR including the recruitment of long-range resection factors and activation of the DNA damage response are also diminished. These phenotypes are correlated with a delay in the eviction of nucleosomes surrounding the DSB. We propose that SWI/SNF orchestrates the recruitment of a pool of MRX that is specifically dedicated to HR.

Authors+Show Affiliations

Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.Department of Biology, University of New Mexico, Albuquerque, NM 87131, USA.Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28398510

Citation

Wiest, Nathaniel E., et al. "The SWI/SNF ATP-dependent Nucleosome Remodeler Promotes Resection Initiation at a DNA Double-strand Break in Yeast." Nucleic Acids Research, vol. 45, no. 10, 2017, pp. 5887-5900.
Wiest NE, Houghtaling S, Sanchez JC, et al. The SWI/SNF ATP-dependent nucleosome remodeler promotes resection initiation at a DNA double-strand break in yeast. Nucleic Acids Res. 2017;45(10):5887-5900.
Wiest, N. E., Houghtaling, S., Sanchez, J. C., Tomkinson, A. E., & Osley, M. A. (2017). The SWI/SNF ATP-dependent nucleosome remodeler promotes resection initiation at a DNA double-strand break in yeast. Nucleic Acids Research, 45(10), 5887-5900. https://doi.org/10.1093/nar/gkx221
Wiest NE, et al. The SWI/SNF ATP-dependent Nucleosome Remodeler Promotes Resection Initiation at a DNA Double-strand Break in Yeast. Nucleic Acids Res. 2017 Jun 2;45(10):5887-5900. PubMed PMID: 28398510.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The SWI/SNF ATP-dependent nucleosome remodeler promotes resection initiation at a DNA double-strand break in yeast. AU - Wiest,Nathaniel E, AU - Houghtaling,Scott, AU - Sanchez,Joseph C, AU - Tomkinson,Alan E, AU - Osley,Mary Ann, PY - 2017/01/24/received PY - 2017/04/06/accepted PY - 2017/4/12/pubmed PY - 2017/9/20/medline PY - 2017/4/12/entrez SP - 5887 EP - 5900 JF - Nucleic acids research JO - Nucleic Acids Res VL - 45 IS - 10 N2 - DNA double-strand breaks (DSBs) are repaired by either the non-homologous end joining (NHEJ) or homologous recombination (HR) pathway. Pathway choice is determined by the generation of 3΄ single-strand DNA overhangs at the break that are initiated by the action of the Mre11-Rad50-Xrs2 (MRX) complex to direct repair toward HR. DSB repair occurs in the context of chromatin, and multiple chromatin regulators have been shown to play important roles in the repair process. We have investigated the role of the SWI/SNF ATP-dependent nucleosome-remodeling complex in the repair of a defined DNA DSB. SWI/SNF was previously shown to regulate presynaptic events in HR, but its function in these events is unknown. We find that in the absence of functional SWI/SNF, the initiation of DNA end resection is significantly delayed. The delay in resection initiation is accompanied by impaired recruitment of MRX to the DSB, and other functions of MRX in HR including the recruitment of long-range resection factors and activation of the DNA damage response are also diminished. These phenotypes are correlated with a delay in the eviction of nucleosomes surrounding the DSB. We propose that SWI/SNF orchestrates the recruitment of a pool of MRX that is specifically dedicated to HR. SN - 1362-4962 UR - https://www.unboundmedicine.com/medline/citation/28398510/The_SWI/SNF_ATP_dependent_nucleosome_remodeler_promotes_resection_initiation_at_a_DNA_double_strand_break_in_yeast_ DB - PRIME DP - Unbound Medicine ER -