The molecular crosstalk between RECQ helicases and associated proteins in human genetic disorders

RECQ helicases involve a family of DNA unwinding enzymes, namely, RECQ1, Bloom syndrome protein, Werner syndrome protein, RECQL4, and RECQ5. These proteins interact with various proteins to form complexes and carry out a range of physiological functions. These genes are involved primarily in molecular pathways such as DNA replication, DNA repair, homologous recombination and telomere maintenance. Dysfunction of these protein complexes leads to chromosomal instability and impaired DNA repair and replication, thus increasing susceptibility to tumor formation. Bloom syndrome protein helicase is characterized by its interaction with proteins such as topoisomerase IIIα and RecQ-mediated genome instability, which prevents excessive sister chromatid exchanges. Werner syndrome protein helicases work in association with enzymes such as Flap Endonuclease 1 and Replication Protein A to maintain telomeric length and resolve secondary structures. RECQL4 helicase acts as a versatile enzyme while initiating DNA replication, carrying out DNA damage repair and contributing to the maintenance of mitochondrial function. The functions and genetic implications of the RECQ1 and RECQ5 helicases have not yet been well established; however, their involvement in DNA repair pathways has been studied. This review outlines the major genetic disorders caused by mutations in the Bloom syndrome protein, Werner syndrome protein and RECQL4 genes, which are associated with Bloom's syndrome, Werner's syndrome and Rothmund-Thomson syndrome, among others. In addition, it explores the roles of RECQ helicases, their molecular interactions in major pathways and their potential as therapeutic targets.