ZNF212 promotes genomic integrity through direct interaction with TRAIP. Issue 2 (3rd January 2023)

• Record Type: Journal Article
• Authors: Chung, Hee Jin; Lee, Joo Rak; Kim, Tae Moon; Kim, Soomi; Park, Kibeom; Kim, Myung-Jin; Jung, Eunyoung; Kim, Subin; Lee, Eun A; Ra, Jae Sun; Hwang, Sunyoung; Lee, Ja Yil; Schärer, Orlando D; Kim, Yonghwan; Myung, Kyungjae; Kim, Hongtae
• Is Part Of: Nucleic acids research. Volume 51:Issue 2(2023)
• Page Start: 631
• Page End: 649
• Publication Date: 2023-01-03
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkac1226
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: TRAIP is a key factor involved in the DNA damage response (DDR), homologous recombination (HR) and DNA interstrand crosslink (ICL) repair. However, the exact functions of TRAIP in these processes in mammalian cells are not fully understood. Here we identify the zinc finger protein 212, ZNF212, as a novel binding partner for TRAIP and find that ZNF212 colocalizes with sites of DNA damage. The recruitment of TRAIP or ZNF212 to sites of DNA damage is mutually interdependent. We show that depletion of ZNF212 causes defects in the DDR and HR-mediated repair in a manner epistatic to TRAIP. In addition, an epistatic analysis of Zfp212, the mouse homolog of human ZNF212, in mouse embryonic stem cells (mESCs), shows that it appears to act upstream of both the Neil3 and Fanconi anemia (FA) pathways of ICLs repair. We find that human ZNF212 interacted directly with NEIL3 and promotes its recruitment to ICL lesions. Collectively, our findings identify ZNF212 as a new factor involved in the DDR, HR-mediated repair and ICL repair though direct interaction with TRAIP.