RecQ family helicases: roles as tumor suppressor proteins.
RecQ family DNA helicases are defined as proteins sharing a homologous region with Escherichia coli RecQ and are basically regarded as enzymes involved in recombination. Humans have five RecQ family members, and deficiencies in three of them, BLM, WRN, and RTS, cause Bloom's, Werner's, and Rothmund-Thomson syndromes, respectively, each characterized by genomic instability and cancer predisposition. In this context, an important function of the RecQ homologs appears to be the unwinding of intermediates of recombination, thereby preventing its uncontrolled execution. As a consequence, their deficiencies give rise to elevated levels of recombination (the hyper-recombination phenotype), which result in chromosomal aberrations including loss of heterozygosity, a common chromosomal change associated with malignancies. Thus, those helicases qualify as caretaker-type tumor suppressor proteins. In addition, BLM and WRN deficiencies have been shown to attenuate p53-mediated apoptosis, suggesting that they also belong to the gatekeeper class of tumor suppressor proteins.
Nakayama
Hiroaki
H
Kyushu University (Emeritus), Hakozaki 6-10-1, Higashi-ku, Fukuoka 812-8581, Japan. nakh@ruby.onc.ne.jp
D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D004247:DNA / Q000378:metabolism; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology; D004261:DNA Replication; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D005090:Exodeoxyribonucleases; D016147:Genes, Tumor Suppressor; D006801:Humans; D008969:Molecular Sequence Data; D053484:RecQ Helicases; D011995:Recombination, Genetic; D017386:Sequence Homology, Amino Acid; D000071657:Werner Syndrome Helicase
D029968:Escherichia coli Proteins; D004247:DNA; D005090:Exodeoxyribonucleases; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; C506725:RECQL protein, human; C506731:RECQL4 protein, human; C506724:RecQ protein, E coli; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase