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

Nam Soo Lee, Hae Ryung Chang, Soomi Kim, Jae Hoon Ji, Joorak Lee, Hyun Ji Lee, Yoojeong Seo, Misun Kang, Joo Seok Han, Kyungjae Myung, Yonghwan Kim, Hongtae Kim

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Cells have evolved sophisticated mechanisms tomaintain 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 theDNA 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 theDDRfrom 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 nonhomologous end joining capability. Taken together, our findings reveal that RNF126 is a novel factor involved in the negative regulation ofDDR,which is important for sustaining genomic integrity.

Original languageEnglish (US)
Pages (from-to)588-598
Number of pages11
JournalJournal of Biological Chemistry
Volume293
Issue number2
DOIs
StatePublished - Jan 12 2018
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Ring finger protein 126 (RNF126) suppresses ionizing radiation-induced p53-binding protein 1 (53BP1) focus formation'. Together they form a unique fingerprint.

Cite this