FLYWCH1, a Multi-Functional Zinc Finger Protein Contributes to the DNA Repair Pathway

Almozyan, Sheema; Coulton, James; Babaei-Jadidi, Roya; Nateri, Abdolrahman S.

Abstract

Over recent years, several Cys2-His2 (C2H2) domain-containing proteins have emerged as critical players in repairing DNA-double strand breaks. Human FLYWCH1 is a newly characterised nuclear transcription factor with (C2H2)-type zinc-finger DNA-binding domains. Yet, our knowledge about FLYWCH1 is still in its infancy. This study explores the expression, role and regulation of FLYWCH1 in the context of DNA damage and repair. We provide evidence suggesting a potential contribution of FLYWCH1 in facilitating the recruitment of DNA-damage response proteins (DDRPs). We found that FLYWCH1 colocalises with ?H2AX in normal fibroblasts and colorectal cancer (CRC) cell lines. Importantly, our results showed that enforced expression of FLYWCH1 induces the expression of ?H2AX, ATM and P53 proteins. Using an ATM-knockout (ATMKO) model, we indicated that FLYWCH1 mediates the phosphorylation of H2AX (Ser139) independently to ATM expression. On the other hand, the induction of DNA damage using UV-light induces the endogenous expression of FLYWCH1. Conversely, cisplatin treatment reduces the endogenous level of FLYWCH1 in CRC cell lines. Together, our findings uncover a novel FLYWCH1/H2AX phosphorylation axis in steady-state conditions and during the induction of the DNA-damage response (DDR). Although the role of FLYWCH1 within the DDR machinery remains largely uncharacterised and poorly understood, we here report for the first-time findings that implicate FLYWCH1 as a potential participant in the DNA damage response signaling pathways.

Citation

Almozyan, S., Coulton, J., Babaei-Jadidi, R., & Nateri, A. S. (2021). FLYWCH1, a Multi-Functional Zinc Finger Protein Contributes to the DNA Repair Pathway. Cells, 10(4), Article 889. https://doi.org/10.3390/cells10040889

• Journal Article Type: Article
• Acceptance Date: Apr 12, 2021
• Online Publication Date: Apr 13, 2021
• Publication Date: Apr 13, 2021
• Deposit Date: Apr 12, 2021
• Publicly Available Date: Apr 14, 2021
• Journal: Cells
• Electronic ISSN: 2073-4409
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 10
• Issue: 4
• Article Number: 889
• DOI: https://doi.org/10.3390/cells10040889
• Keywords: FLYWCH1; Cys2-His2 (C2H2)-type zinc-finger; DNA-damage response; ?H2AX; ATM; 31 p53; CRC 32 33
• Public URL: https://nottingham-repository.worktribe.com/output/5461265
• Publisher URL: https://www.mdpi.com/2073-4409/10/4/889