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Almozyan, Sheema; Coulton, James; Babaei-Jadidi, Roya; Nateri, Abdolrahman S
FLYWCH1, a multi-functional zinc finger protein contributes to the DNA repair pathway Journal Article
In: Cells, vol. 10, no. 4, pp. 889, 2021.
Abstract | Tags: ATM, CRC, Cys2-His2 (C2H2)-type zinc-finger, DNA-damage response, FLYWCH1, p53, γH2AX
@article{Almozyan2021-jt,
title = {FLYWCH1, a multi-functional zinc finger protein contributes to
the DNA repair pathway},
author = {Sheema Almozyan and James Coulton and Roya Babaei-Jadidi and Abdolrahman S Nateri},
year = {2021},
date = {2021-04-01},
journal = {Cells},
volume = {10},
number = {4},
pages = {889},
publisher = {MDPI AG},
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
γH2AX in normal fibroblasts and colorectal cancer (CRC)
cell lines. Importantly, our results showed that enforced
expression of FLYWCH1 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 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.},
keywords = {ATM, CRC, Cys2-His2 (C2H2)-type zinc-finger, DNA-damage response, FLYWCH1, p53, γH2AX},
pubstate = {published},
tppubtype = {article}
}
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