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J Biol Chem. 2018 Jan 12;293(2):588-598. doi: 10.1074/jbc.M116.765602. Epub 2017 Nov 22.

Ring finger protein 126 (RNF126) suppresses ionizing radiation-induced p53-binding protein 1 (53BP1) focus formation.

Author information

1
From the Department of Biological Sciences, Sungkyunkwan University, Suwon 16419, Republic of Korea.
2
the Department of Biological Sciences, Sookmyung Women's University, Seoul 04310, Republic of Korea.
3
the Genomic Instability Research Center, Ajou University School of Medicine, Suwon 16499, Republic of Korea.
4
the Center for Genomic Integrity, Institute for Basic Science, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea, and.
5
the Department of Biological Sciences, Sookmyung Women's University, Seoul 04310, Republic of Korea, yhkim@sookmyung.ac.kr.
6
From the Department of Biological Sciences, Sungkyunkwan University, Suwon 16419, Republic of Korea, khtcat@skku.edu.
7
the Center for Neuroscience Imaging Research, Institute for Basic Science, Sungkyunkwan University, Suwon 16419, Republic of Korea.

Abstract

Cells have evolved sophisticated mechanisms to maintain genomic integrity in response to DNA damage. Ionizing radiation (IR)-induced DNA damage results in the formation of IR-induced foci (iRIF) in the nucleus. The iRIF formation is part of the DNA damage response (DDR), which is an essential signaling cascade that must be strictly regulated because either the loss of or an augmented DDR leads to loss of genome integrity. Accordingly, negative regulation of the DDR is as critical as its activation. In this study, we have identified ring finger protein 126 (RNF126) as a negative regulator of the DDR from a screen of iRIF containing 53BP1. RNF126 overexpression abolishes not only the formation of 53BP1 iRIF but also of RNF168, FK2, RAP80, and BRCA1. However, the iRIF formation of γH2AX, MDC1, and RNF8 is maintained, indicating that RNF126 acts between RNF8 and RNF168 during the DDR. In addition, RNF126 overexpression consistently results in the loss of RNF168-mediated H2A monoubiquitination at lysine 13/15 and inhibition of the non-homologous end joining capability. Taken together, our findings reveal that RNF126 is a novel factor involved in the negative regulation of DDR, which is important for sustaining genomic integrity.

KEYWORDS:

DNA damage; DNA damage response; histone modification; signal transduction; ubiquitylation (ubiquitination)

PMID:
29167269
PMCID:
PMC5767864
DOI:
10.1074/jbc.M116.765602
[Indexed for MEDLINE]
Free PMC Article

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