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Zinc finger protein 827 (ZNF827)
- Target
- ZNF827
- Molecular classification
- Transcription factor, C2H2 zinc finger protein, ssDNA-binding protein, Component of chromatin remodeling complexes
01
Overview
Zinc finger protein 827 (ZNF827) is a C2H2-type zinc finger transcription factor that functions as a single-stranded DNA (ssDNA) binding protein and a component of the ATR-CHK1 DNA damage response pathway. ZNF827 accumulates at stalled replication forks and sites of DNA damage, where it binds ssDNA and facilitates the activation of ATR signaling, promoting homologous recombination-mediated DNA repair. It is essential for replication initiation, fork progression, and cell cycle progression at the G1/S transition. ZNF827 also plays an important role in telomere maintenance via recruitment of the nucleosome remodeling and deacetylase (NuRD) complex, particularly in cancer cells using the alternative lengthening of telomeres (ALT) pathway, and is involved in chromatin remodeling and the regulation of neuronal differentiation-related genes. Depletion of ZNF827 sensitizes cancer cells to topoisomerase inhibitors, highlighting its potential as a therapeutic target in cancers with replication stress or active ALT pathways.
- Other names
- ZNF827Zinc finger protein 827
02
Mechanism of action
Inhibition or depletion of ZNF827 sensitizes cells to DNA-damaging agents (topoisomerase inhibitors) by suppressing ATR-CHK1-mediated DNA repair and homologous recombination
03
Biological functions
DNA repair (particularly homologous recombination)DNA damage response (ATR-CHK1 pathway activation)Telomere maintenance (especially in ALT pathway)Chromatin remodelingNegative regulation of shelterin complex assemblyRegulation of neuronal differentiation-related gene transcription
04
Disease associations
Cancer (especially those using the alternative lengthening of telomeres [ALT] pathway)Genome instability disorders
05
Safety considerations
Potential effects on genome stability if inhibited in normal cellsImpaired DNA repair may increase genotoxic risk in proliferating tissues
06
Interacting drugs
Topotecan (sensitization observed upon ZNF827 depletion)
07
Biomarkers
ZNF827 expression may serve as biomarker for ALT pathway activity in cancersZNF827 depletion coupled with cell cycle arrest markers (e.g., p21 accumulation)
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