Chromodomain-helicase-DNA-binding protein 1 (CHD1) (CHD1)

Chromodomain-helicase-DNA-binding protein 1 (CHD1) is an ATP-dependent chromatin remodeling enzyme that is essential for maintaining the structural integrity of the genome and regulating gene expression (UniProt: P40201). It functions by binding to methylated histone H3 lysine 4 (H3K4me3), a hallmark of active transcription, and utilizing its ATPase activity to slide or eject nucleosomes, thereby facilitating the access of transcriptional machinery and DNA repair proteins to the DNA template (PubMed: 28263199). In clinical oncology, CHD1 is recognized as a significant tumor suppressor, particularly in prostate cancer, where its loss is one of the most frequent genomic alterations, occurring in approximately 10-15% of primary tumors (PubMed: 30385745). The loss of CHD1 leads to a deficiency in homologous recombination repair (HRR), creating a therapeutic vulnerability known as synthetic lethality. This vulnerability is exploited by PARP inhibitors, such as Olaparib and Talazoparib, which are currently being evaluated in clinical trials for patients with CHD1-deficient cancers (ClinicalTrials.gov: NCT02854436). Beyond its role in DNA repair, CHD1 also influences androgen receptor (AR) signaling and RNA splicing, making it a multifaceted target for precision medicine strategies.

Other names

CHD-1ATP-dependent helicase CHD1Chromodomain-helicase-DNA-binding protein 1

Induction of synthetic lethality in CHD1-deficient cells through PARP inhibition, which exploits defects in homologous recombination repair.