WD repeat and HMG-box DNA binding protein 1 (WDHD1)

WD repeat and HMG-box DNA binding protein 1 (WDHD1) is a multifunctional **DNA-binding protein** and essential core **component of the DNA replisome**, characterized by N-terminal WD40 repeat domains and a C-terminal HMG box[1][3][5]. It mediates **protein–protein interactions** crucial for DNA replication initiation, fork progression, sister chromatid cohesion, and genome stability, linking the CMG helicase complex to DNA polymerase α[1][3]. WDHD1 is conserved from yeast to humans, where it is homologous to yeast CTF4[1]. Dysregulation or overexpression of WDHD1 has been strongly implicated in the **development, progression, and therapy resistance** of multiple cancers, making it a promising research target for cancer therapy and biomarker development[1]. No direct pharmacological inhibitors are currently in clinical use, but WDHD1 suppression sensitizes tumors to chemoradiotherapy and may modulate important pathways like PI3K/AKT and JAK-STAT[1].

Other names

AND-1AND1CTF4CHTF4Acidic nucleoplasmic DNA-binding protein 1Chromosome transmission fidelity factor 4 homolog

Targeting WDHD1 (e.g., by knockdown or inhibition) sensitizes tumor cells to radiation and chemotherapeutic agents by impairing DNA replication and repair machinery, leading to decreased tumor cell proliferation and increased genome instability[1].