Mutations in conserved functional domains of human RecQ helicases are associated with diseases and cancer: A review

Abstract

RecQ helicases belong to a ubiquitous family of DNA unwinding enzymes that are essential to maintain genome stability by acting at the interface between DNA replication, recombination, and repair. Humans have five different paralogues of RecQ helicases namely RecQ1, BLM, WRN, RecQ4, and RecQ5. Germ-line mutations in these helicases give rise to distinct human genetic disorders, Bloom Syndrome, Werner Syndrome, Rothmund-Thomson, RAPADILINO, and Baller-Gerold syndromes. Other than distinct clinical symptoms, all these genetic disorders show a predisposition to cancer. While the three paralogues BLM, WRN, and RecQ4 are directly associated with syndromes, loss of function of RecQ1 and RecQ5 are also emerging to be causative of various types of cancer. This review summarizes the domain architecture of RecQ helicases and the mutations that are associated with various diseases. Here we observe the occurrence of disease-causing mutations mainly in the catalytic regions of the proteins, and that some of these mutations are common between the respective disorders and cancer. Furthermore, this review discusses the results of several reports that study the role of residues with disease-causing mutations. It also overviews the research focusing on RecQ helicases as potential targets for cancer therapy.

Keywords: Cancer; Genetic disorders; Mutational spectrum; Protein domains; Protein functions; RecQ helicases.