Premature aging and predisposition to cancers caused by mutations in RecQ family helicases.
DNA helicases, because they unwind duplex DNA, have important roles in cellular DNA events such as replication, recombination, repair, and transcription. Multiple DNA helicase families with seven consensus motifs have been found, and members within each helicase family also share sequence homologies between motifs. The RecQ helicase family includes helicases that have extensive amino acid sequence homologies to the E. coli DNA helicase RecQ, which has been implicated in double-strand break repair and suppression of illegitimate recombination. To date, five RecQ helicase species exist in humans, but their exact biological functions remain unknown. In this paper, on the basis of five years of work, I overview the updated molecular biology of five human RecQ helicases; genetic diseases such as Werner's, Bloom's, and Rothmund-Thomson's syndromes caused by helicase mutations; the associated premature aging phenotype; and an increased risk of neoplasms. I also describe a hypothesis of "tissue-specific genomic instability" that accounts for the pathology behind multisymptomatic RecQ helicase syndromes.
Furuichi
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Y
AGENE Research Institute, Kamakura, Japan. furuichi@agene.co.jp
D021581:Active Transport, Cell Nucleus; D000251:Adenosine Triphosphatases / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D019588:Aging, Premature / Q000201:enzymology / Q000235:genetics*; D000818:Animals; D001816:Bloom Syndrome / Q000201:enzymology / Q000235:genetics; D002467:Cell Nucleus / Q000201:enzymology; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002877:Chromosomes, Human / Q000235:genetics; D016384:Consensus Sequence; D004265:DNA Helicases / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics; D004790:Enzyme Induction; D005090:Exodeoxyribonucleases; D020022:Genetic Predisposition to Disease; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D018345:Mice, Knockout; D005810:Multigene Family; D009386:Neoplastic Syndromes, Hereditary / Q000201:enzymology / Q000235:genetics*; D009928:Organ Specificity; D010641:Phenotype; D053484:RecQ Helicases; D011038:Rothmund-Thomson Syndrome / Q000201:enzymology / Q000235:genetics; D012854:Sister Chromatid Exchange / Q000235:genetics; D014898:Werner Syndrome / Q000201:enzymology / Q000235:genetics; D000071657:Werner Syndrome Helicase
C506732:RECQL5 protein, human; D005090:Exodeoxyribonucleases; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; C506731:RECQL4 protein, human; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase