Helicases and human diseases

Recent progress in pharmaceutical sciences has made it possible for us to live longer and longer. For example, antibiotics and vaccines have been developed that were successfully administered to patients with infectious diseases. A number of effective drugs for specific diseases could be purified from natural resources or created by chemical synthesis, and recent recombinant DNA technologies have brought about antibody-drugs. It seems increasingly possible that a treatment for every disease could be established in the near future. Nevertheless, prevention or remedies for inherited age-related diseases, including cancer, have not yet been completely established. However, recent progresses in human genetics and molecular biology revealed that premature aging is caused by mutations on DNA helicase encoding genes (Bernstein et al., 2010). These exciting findings have encouraged scientists to research mechanisms of the age-related diseases. DNA/RNA helicases are enzymes that unwind DNA/DNA, DNA/RNA, and RNA/RNA duplexes to execute and regulate DNA replication, recombination, repair, and transcription (Patel and Donmez, 2006). To date, numerous genes have been identified to encode helicases. Importantly, genetic studies have revealed that mutations in some of these genes are associated with certain human diseases, including Xeroderma Pigmentosum (XP), Cockayne Syndrome (CS), and Werner Syndrome (WS) (Puzianowska-Kuznicka and Kuznicki, 2005). Given that helicases play an important role in the regulation and maintenance of chromosomal DNAs, it might not be so difficult to understand that their dysfunction leads to unfavorable states. Nuclear events, such as nucleotide excision repair (NER), transcription coupled repair (TCR), and telomere maintenance, are thought to be individually affected by XPB/XPD, CSA/CSB and WRN helicases, respectively (Table 1). Because epigenetic changes and disruption of chromosomal integrity have been strongly suggested to correlate with cellular senescence, these helicases may be important factors to regulate aging and age-related diseases. Despite great efforts being made to elucidate the properties of helicases on a molecular and cellular level, it seems that the gap from molecule to patient is still distant. In this research topic, authors have described and discussed the forefront of the helicase studies. It is very important to establish a molecular model of how helicases interact with DNA repair machinery. In the research topic, the properties of the FANCJ (BRIP1) that affect cancer and Fanconi Anemia (FA) development have been summarized (Brosh and Cantor, 2014). In order to assess the mechanisms of diseases, including cancer, which are caused by dysfunctions of helicases, Table 1 | Helicases that associate with human diseases.