Abstract
Maintaining genomic integrity is critical for sustaining individual animals and passing on the genome to subsequent generations. Several enzymes, such as DNA helicases and DNA polymerases, are involved in maintaining genomic integrity by unwinding and synthesizing the genome, respectively. Indeed, several human diseases that arise caused by deficiencies in these enzymes have long been known. In this review, the author presents the DNA helicases associated with human diseases discovered to date using recent analyses, including exome sequences. Since several mouse models that reflect these human diseases have been developed and reported, this study also summarizes the current knowledge regarding the outcomes of DNA helicase deficiencies in humans and mice and discusses possible mechanisms by which DNA helicases maintain genomic integrity in mammals. It also highlights specific diseases that demonstrate mammalian resilience, in which, despite the presence of genomic instability, patients and mouse models have lifespans comparable to those of the general population if they do not develop cancers; finally, this study discusses future directions for therapeutic applications in humans that can be explored using these mouse models.