Structure-function analysis of DNA helicase HELQ: A new diagnostic marker in ovarian cancer

It has been previously reported that a deficiency of the helicase, POLQ-like (HELQ) gene increases the risk of ovarian cancer. The present study aimed to explore the structure-function association of HELQ and discuss the effect of molecular structure on the occurrence of tumors. ExPASy tools were employed to analyze the physicochemical properties and secondary structure of the genes. PHYRE2 Protein Fold Recognition Server was used to construct the three-dimensional model and find the ligand-binding sites of HELQ. In addition, the potential functions corresponding to these structures were excavated by comparing and analyzing protein domains. The HELQ protein is located in the cytoplasm (56.5%) and nucleus (21.7%). HELQ has 4 conserved domains, consisting of DEXDc, HELICc, HHH_5 and PRK02362, which contain the adenosine triphosphate (ATP) binding site, nucleotide binding region and putative Mg2+ binding site. In the secondary structure, it was found that HELQ was mainly composed of α helix (46.68%) and random coils (43.05%), with only 10.26% extended strand. According to 3DLigandSite Server, the ligand binding sites appeared in ILE333, LYS335, TYR337, SER362, LEU367, LYS397, GLN340, GLY363, GLY364 and ASN678 of the amino acid sequence. Among the functional protein association networks, regulator of telomere elongation helicase 1, family with sequence similarity 175 member A, small ubiquitin-like modifier 1, DNA polymerase ν and coiled-coil domain containing 158 were involved and co-expressed with HELQ. PredictProtein analysis indicated that the dominant functions of HELQ were ATP-dependent helicase activity and participation in the DNA repair process. Characteristics of the HELQ protein were obtained by bioinformatics analysis, based on which the role of HELQ in DNA replication, DNA repair and maintenance of genomic stability was explored. It was concluded that modulation the function of HELQ helicase may be used in the treatment of ovarian cancer.