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DNA Helicases Associated with Genetic Instability, Cancer, and Aging

  • Avvaru N. Suhasini
  • Robert M. BroshJr.
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 973)

Abstract

DNA helicases have essential roles in the maintenance of genomic ­stability. They have achieved even greater prominence with the discovery that mutations in human helicase genes are responsible for a variety of genetic disorders and are associated with tumorigenesis. A number of missense mutations in human helicase genes are linked to chromosomal instability diseases characterized by age-related disease or associated with cancer, providing incentive for the characterization of molecular defects underlying aberrant cellular phenotypes. In this chapter, we discuss some examples of clinically relevant missense mutations in various human DNA helicases, particularly those of the Iron-Sulfur cluster and RecQ families. Clinically relevant mutations in the XPD helicase can lead to Xeroderma pigmentosum, Cockayne’s syndrome, Trichothiodystrophy, or COFS syndrome. FANCJ mutations are associated with Fanconi anemia or breast cancer. Mutations of the Fe-S helicase ChlR1 (DDX11) are linked to Warsaw Breakage syndrome. Mutations in the RecQ helicases BLM and WRN are linked to the cancer-prone disorder Bloom’s syndrome and premature aging condition Werner syndrome, respectively. RECQL4 mutations can lead to Rothmund-Thomson syndrome, Baller-Gerold syndrome, or RAPADILINO. Mutations in the Twinkle mitochondrial helicase are responsible for several neuromuscular degenerative disorders. We will discuss some insights gained from biochemical and genetic studies of helicase variants, and highlight some hot areas of helicase research based on recent developments.

Keywords

Nucleotide Excision Repair Fanconi Anemia Xeroderma Pigmentosum Helicase Activity Werner Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This research was supported by the Intramural Research Program of the NIH, National Institute on Aging and the Fanconi Anemia Research Fund (RMB). We apologize to helicase researchers whose work was not cited due to space limitations.

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of HealthNIH Biomedical Research CenterBaltimoreUSA

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