Flywch1, a multi‐functional zinc finger protein contributes to the DNA repair pathway

Sheema Almozyan, James Coulton, Roya Babaei‐jadidi, Abdolrahman S. Nateri

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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 character-ised 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 γH2AX in normal fibroblasts and colo-rectal cancer (CRC) cell lines. Importantly, our results showed that enforced expression of FLY‐ WCH1 induces the expression of γH2AX, 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 unchar-acterised 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.

Original languageEnglish
Article number889
JournalCells
Volume10
Issue number4
DOIs
StatePublished - Apr 2021
Externally publishedYes

Keywords

  • ATM
  • CRC
  • Cys2‐His2 (C2H2)‐type zinc‐finger
  • DNA‐damage response
  • FLYWCH1
  • P53
  • γH2AX

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