In silico analyses of a new group of fungal and plant RecQ4-homologous proteins

Abstract

Bacterial and eukaryotic RecQ helicases comprise a family of homologous proteins necessary for maintaining genomic integrity during the cell cycle and DNA repair. There is one known bacterial RecQ helicase, and five eukaryotic RecQ helicases that have been described: RecQ1p, RecQ4p, RecQ5p, Bloom, and Werner. While the biochemical functions of Bloom and Werner helicases are well understood, the same is not true for RecQ4p helicase. RecQ4p mutations lead to pathologies like Rothmund–Thompson syndrome (RTS), RAPADILINO, and Baller–Gerold syndrome (BGS). Until now, RecQ4p helicases had only been described in metazoans, and their presence in organisms like fungi and plants were not known. Thus far only one RecQ-homologous protein (Sgs1p), similar to Bloom helicase, has been described in fungal genomes. In the present study we employed an in silico approach, and successfully identified and characterized a second RecQ helicase from the genomes of different fungal and two plant species that shows similarity to metazoan RecQ4 proteins. An in-depth phylogenetic analysis of these new fungal and plant RecQ4-like sequences (termed Hrq1p) indicated that they are orthologous to the metazoan RecQ4p. We employed hydrophobic cluster analysis (HCA) and three-dimensional modeling of selected Hrq1p sequences to compare conserved regions among Hrq1p, human RecQ4p and bacterial RecQp. The results indicated that Hrq1p sequences, as previously observed for metazoan RecQ4 proteins, probably act in genomic maintenance and/or chromatin remodeling in fungal and plant cells.