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Role of the yeast DNA repair protein Nej1 in end processing during the repair of DNA double strand breaks by non-homologous end joining.
DNA Repair (Amst). 2015 Jul; 31:1-10.DR

Abstract

DNA double strand breaks (DSB)s often require end processing prior to joining during their repair by non-homologous end joining (NHEJ). Although the yeast proteins, Pol4, a Pol X family DNA polymerase, and Rad27, a nuclease, participate in the end processing reactions of NHEJ, the mechanisms underlying the recruitment of these factors to DSBs are not known. Here we demonstrate that Nej1, a NHEJ factor that interacts with and modulates the activity of the NHEJ DNA ligase complex (Dnl4/Lif1), physically and functionally interacts with both Pol4 and Rad27. Notably, Nej1 and Dnl4/Lif1, which also interacts with both Pol4 and Rad27, independently recruit the end processing factors to in vivo DSBs via mechanisms that are additive rather than redundant. As was observed with Dnl4/Lif1, the activities of both Pol4 and Rad27 were enhanced by the interaction with Nej1. Furthermore, Nej1 increased the joining of incompatible DNA ends in reconstituted reactions containing Pol4, Rad27 and Dnl4/Lif1, indicating that the stimulatory activities of Nej1 and Dnl4/Lif1 are also additive. Together our results reveal novel roles for Nej1 in the recruitment of Pol4 and Rad27 to in vivo DSBs and the coordination of the end processing and ligation reactions of NHEJ.

Authors+Show Affiliations

Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 14N, Canada.Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.Department of Internal Medicine, University of New Mexico Cancer Center, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA. Electronic address: atomkinson@salud.unm.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25942368

Citation

Yang, Hui, et al. "Role of the Yeast DNA Repair Protein Nej1 in End Processing During the Repair of DNA Double Strand Breaks By Non-homologous End Joining." DNA Repair, vol. 31, 2015, pp. 1-10.
Yang H, Matsumoto Y, Trujillo KM, et al. Role of the yeast DNA repair protein Nej1 in end processing during the repair of DNA double strand breaks by non-homologous end joining. DNA Repair (Amst). 2015;31:1-10.
Yang, H., Matsumoto, Y., Trujillo, K. M., Lees-Miller, S. P., Osley, M. A., & Tomkinson, A. E. (2015). Role of the yeast DNA repair protein Nej1 in end processing during the repair of DNA double strand breaks by non-homologous end joining. DNA Repair, 31, 1-10. https://doi.org/10.1016/j.dnarep.2015.04.003
Yang H, et al. Role of the Yeast DNA Repair Protein Nej1 in End Processing During the Repair of DNA Double Strand Breaks By Non-homologous End Joining. DNA Repair (Amst). 2015;31:1-10. PubMed PMID: 25942368.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of the yeast DNA repair protein Nej1 in end processing during the repair of DNA double strand breaks by non-homologous end joining. AU - Yang,Hui, AU - Matsumoto,Yoshihiro, AU - Trujillo,Kelly M, AU - Lees-Miller,Susan P, AU - Osley,Mary Ann, AU - Tomkinson,Alan E, Y1 - 2015/04/21/ PY - 2015/01/26/received PY - 2015/04/06/revised PY - 2015/04/13/accepted PY - 2015/5/6/entrez PY - 2015/5/6/pubmed PY - 2016/3/26/medline KW - DNA damage KW - DNA double-strand break KW - DNA ligase KW - DNA nuclease KW - DNA polymerase KW - Genomic instability KW - Protein–protein interaction SP - 1 EP - 10 JF - DNA repair JO - DNA Repair (Amst) VL - 31 N2 - DNA double strand breaks (DSB)s often require end processing prior to joining during their repair by non-homologous end joining (NHEJ). Although the yeast proteins, Pol4, a Pol X family DNA polymerase, and Rad27, a nuclease, participate in the end processing reactions of NHEJ, the mechanisms underlying the recruitment of these factors to DSBs are not known. Here we demonstrate that Nej1, a NHEJ factor that interacts with and modulates the activity of the NHEJ DNA ligase complex (Dnl4/Lif1), physically and functionally interacts with both Pol4 and Rad27. Notably, Nej1 and Dnl4/Lif1, which also interacts with both Pol4 and Rad27, independently recruit the end processing factors to in vivo DSBs via mechanisms that are additive rather than redundant. As was observed with Dnl4/Lif1, the activities of both Pol4 and Rad27 were enhanced by the interaction with Nej1. Furthermore, Nej1 increased the joining of incompatible DNA ends in reconstituted reactions containing Pol4, Rad27 and Dnl4/Lif1, indicating that the stimulatory activities of Nej1 and Dnl4/Lif1 are also additive. Together our results reveal novel roles for Nej1 in the recruitment of Pol4 and Rad27 to in vivo DSBs and the coordination of the end processing and ligation reactions of NHEJ. SN - 1568-7856 UR - https://www.unboundmedicine.com/medline/citation/25942368/Role_of_the_yeast_DNA_repair_protein_Nej1_in_end_processing_during_the_repair_of_DNA_double_strand_breaks_by_non_homologous_end_joining_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1568-7864(15)00087-7 DB - PRIME DP - Unbound Medicine ER -