Distinct roles of RECQ1 in the maintenance of genomic stability

Abstract

Five human RecQ helicases (WRN, BLM, RECQ4, RECQ5, RECQ1) exist in humans. Of these, three are genetically linked to diseases of premature aging and/or cancer. Neither RECQ1 nor RECQ5 has yet been implicated in a human disease. However, cellular studies and genetic analyses of model organisms indicate that RECQ1 (and RECQ5) play an important role in the maintenance of genomic stability. Biochemical studies of purified RECQ1 protein demonstrate that the enzyme catalyzes DNA unwinding and strand annealing, and these activities are likely to be important for its role in DNA repair. RECQ1 also physically and functionally interacts with proteins involved in genetic recombination. In this review, we will summarize our current knowledge of RECQ1 roles in cellular nucleic acid metabolism and propose avenues of investigation for future studies.

Fig. 1. Alignment and phylogenetic tree of RECQ1-like helicases across species

Panel A, The conserved helicase core domain is indicated by yellow, the RecQ C-terminal domain (RQC) in purple, and the Helicase and RNase D C-terminal domain (HRDC) in green. Panel B, The amino acid sequences of the full length proteins in Panel A were aligned and a phylogenetic tree was constructed by ClustalX2 with number of bootstrap trials at 1000. The image was generated in Treeview. Branch numbers refer to bootstrap values.

Fig. 1. Alignment and phylogenetic tree of RECQ1-like helicases across species

Panel A, The conserved helicase core domain is indicated by yellow, the RecQ C-terminal domain (RQC) in purple, and the Helicase and RNase D C-terminal domain (HRDC) in green. Panel B, The amino acid sequences of the full length proteins in Panel A were aligned and a phylogenetic tree was constructed by ClustalX2 with number of bootstrap trials at 1000. The image was generated in Treeview. Branch numbers refer to bootstrap values.

Fig. 2. Nucleotide-induced conformational switch controls RECQ1 helicase and strand annealing activities

A model is presented depicting the importance of ATP-induced conformational change in RECQ1 for regulation of its catalytic activity as a DNA helicase or strand annealing protein. Assembly state of RECQ1 in terms of oligomerization is not depicted in the model.

Fig. 3. Potential cellular functions of RECQ1 in DNA metabolism

See text for details.