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Article

Karyopherin α-2 Mediates MDC1 Nuclear Import through a Functional Nuclear Localization Signal in the tBRCT Domain of MDC1

1
Laboratory of Genomic Instability and Cancer therapeutics, Cancer Mutation Research Center, Chosun University, Gwangju 61452, Korea
2
Department of Premedical Sciences, College of Medicine, Chosun University, Gwangju 61452, Korea
3
Department of Neurosurgery, College of Medicine, Chosun University, Gwangju 61452, Korea
4
Department of Cellular and Molecular Medicine, College of Medicine, Chosun University, Gwangju 61452, Korea
5
Department of Anatomy, College of Medicine, Chosun University, Gwangju 61452, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(7), 2650; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072650
Received: 19 March 2020 / Revised: 6 April 2020 / Accepted: 8 April 2020 / Published: 10 April 2020
(This article belongs to the Section Molecular Genetics and Genomics)
Mediator of DNA damage checkpoint protein 1 (MDC1) plays a vital role in DNA damage response (DDR) by coordinating the repair of double strand breaks (DSBs). Here, we identified a novel interaction between MDC1 and karyopherin α-2 (KPNA2), a nucleocytoplasmic transport adaptor, and showed that KPNA2 is necessary for MDC1 nuclear import. Thereafter, we identified a functional nuclear localization signal (NLS) between amino acid residues 1989–1994 of the two Breast Cancer 1 (BRCA1) carboxyl-terminal (tBRCT) domain of MDC1 and demonstrated disruption of this NLS impaired interaction between MDC1 and KPNA2 and reduced nuclear localization of MDC1. In KPNA2-depleted cells, the recruitment of MDC1, along with the downstream signaling p roteins Ring Finger Protein 8 (RNF8), 53BP1-binding protein 1 (53BP1), BRCA1, and Ring Finger Protein 168 (RNF168), to DNA damage sites was abolished. Additionally, KPNA2-depleted cells had a decreased rate of homologous recombination (HR) repair. Our data suggest that KPNA2-mediated MDC1 nuclear import is important for DDR signaling and DSB repair. View Full-Text
Keywords: MDC1; KPNA2; DNA damage response; homologous recombination repair; nuclear import MDC1; KPNA2; DNA damage response; homologous recombination repair; nuclear import
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MDPI and ACS Style

Radhakrishnan, K.; Park, S.-J.; Kim, S.W.; Hariharasudhan, G.; Jeong, S.-Y.; Chang, I.Y.; Lee, J.-H. Karyopherin α-2 Mediates MDC1 Nuclear Import through a Functional Nuclear Localization Signal in the tBRCT Domain of MDC1. Int. J. Mol. Sci. 2020, 21, 2650. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072650

AMA Style

Radhakrishnan K, Park S-J, Kim SW, Hariharasudhan G, Jeong S-Y, Chang IY, Lee J-H. Karyopherin α-2 Mediates MDC1 Nuclear Import through a Functional Nuclear Localization Signal in the tBRCT Domain of MDC1. International Journal of Molecular Sciences. 2020; 21(7):2650. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072650

Chicago/Turabian Style

Radhakrishnan, Kamalakannan; Park, Seon-Joo; Kim, Seok W.; Hariharasudhan, Gurusamy; Jeong, Seo-Yeon; Chang, In Y.; Lee, Jung-Hee. 2020. "Karyopherin α-2 Mediates MDC1 Nuclear Import through a Functional Nuclear Localization Signal in the tBRCT Domain of MDC1" Int. J. Mol. Sci. 21, no. 7: 2650. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072650

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