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

Abstract

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.

The HelQ human DNA repair helicase utilizes a PWI-like domain for DNA loading through interaction with RPA, triggering DNA unwinding by the HelQ helicase core

“…The cellular response to ICLs is an area of great interest, because ICLs are highly toxic biproducts of natural cellular chemistry and they are used in drug therapies against cancerous cells. The protective effect of HelQ against ICLs in healthy cells is also a factor promoting resistance to their use as treatments ( 21 , 22 ), but new knowledge about the molecular mechanisms of HelQ can be developed into ways of overcoming this problem, alongside other emerging helicase targets ( 72 ).…”

“…In U2OS cells cancer phenotypes are triggered by Δ helq ( 19 ), and copy number variations in helq are associated with ovarian cancers ( 3 , 20 ). In addition, over-expression of HelQ promotes resistance to treatments for ovarian cancers that are based on use of DNA crosslinkers ( 21 , 22 ), implicating HelQ levels in cells as potential factor to be overcome in hard-to-treat cancers. Overall, genetic analysis of helq and cancer association studies implicate HelQ helicase in recovery of DNA replication that is stressed or broken by endogenous or environmental stresses, arising in ways that are reviewed recently in references ( 23 , 24 ).…”

Sensitive Detection of Gas-Phase Glyoxal by Electron Attachment Reaction Ionization Mass Spectrometry

“…Preparation of Gas Samples. A standard gas generator reported by Liu et al 53 was used to prepare gaseous GLY samples of stable concentrations. The detailed preparation procedures are as follows.…”

Helicase POLQ-like (HELQ) as a novel indicator of platinum-based chemoresistance for epithelial ovarian cancer

“…Furthermore, the efficacy of HR shows a 50-60% decrease in HELQ-knockout mice with increasing sensitivity to poly ADP-ribose polymerase (PARP) inhibitors [17]. Therefore, HELQ may also be a strong candidate for screening chemo-sensitive EOC and may provide, like the BRCA gene, groundbreaking ideas for the clinical treatment in human cancer [20,21]. However, the role and molecular mechanisms of HELQ in chemo-sensitivity remain largely unknown in EOC.…”