Article

Human RECQ helicases: roles in DNA metabolism, mutagenesis and cancer biology.

Department of Pathology, University of Washington, Seattle, WA 98195-7705, USA.
Seminars in Cancer Biology (Impact Factor: 7.44). 10/2010; 20(5):329-39. DOI: 10.1016/j.semcancer.2010.10.002
Source: PubMed

ABSTRACT Helicases use the energy of ATP hydrolysis to separate double-stranded nucleic acids to facilitate essential processes such as replication, recombination, transcription and repair. This article focuses on the human RECQ helicase gene and protein family. Loss of function of three different members has been shown to cause Bloom syndrome (BS), Werner syndrome (WS) and Rothmund-Thomson syndrome (RTS). This article outlines clinical and cellular features of these cancer predisposition syndromes, and discusses their pathogenesis in light of our understanding of RECQ helicase biochemical activities and in vivo functions. I also discuss the emerging role for RECQ helicases as predictors of disease risk and the response to therapy.

0 Bookmarks
 · 
119 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bloom syndrome (BS) is an inherited genomic instability disorder caused by disruption of the BLM helicase and confers an extreme cancer predisposition. Here we report on a girl with BS who developed acute lymphoblastic leukaemia (ALL) at age nine, and treatment-related acute myeloid leukaemia (t-AML) aged 12. She was compound heterozygous for the novel BLM frameshift deletion c.1624delG and the previously described c.3415C>T nonsense mutation. Two haematological malignancies in a child with BS imply a fundamental role for BLM for normal haematopoiesis, in particular in the presence of genotoxic stress.
    Journal of genetic syndromes & gene therapy. 09/2013; 4(8).
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hrq1 helicase is a novel member of the RecQ family. Among the five human RecQ helicases, Hrq1 is most homologous to RECQL4 and is conserved in fungal genomes. Recent genetic and biochemical studies have shown that it is a functional gene, involved in the maintenance of genome stability. To better define the roles of Hrq1 in yeast cells, we investigated genetic interactions between HRQ1 and several DNA repair genes. Based on DNA damage sensitivities induced by 4-nitroquinoline-1-oxide (4-NQO) or cisplatin, RAD4 was found to be epistatic to HRQ1. On the other hand, mutant strains defective in either homologous recombination (HR) or post-replication repair (PRR) became more sensitive by additional deletion of HRQ1, indicating that HRQ1 functions in the RAD4-dependent nucleotide excision repair (NER) pathway independent of HR or PRR. In support of this, yeast two-hybrid analysis showed that Hrq1 interacted with Rad4, which was enhanced by DNA damage. Overexpression of Hrq1K318A helicase-deficient protein rendered mutant cells more sensitive to 4-NQO and cisplatin, suggesting that helicase activity is required for the proper function of Hrq1 in NER.
    The Journal of Microbiology 04/2014; 52(4):292-8. · 1.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: RecQ DNA helicases are key enzymes in the maintenance of genome integrity, and they have functions in DNA replication, recombination, and repair. In contrast to most RecQs, RecQ from Deinococcus radiodurans (DrRecQ) possesses an unusual domain architecture that is crucial for its remarkable ability to repair DNA. Here, we determined the crystal structures of the DrRecQ helicase catalytic core and its ADP-bound form, revealing interdomain flexibility in its first RecA-like and winged-helix (WH) domains. Additionally, the WH domain of DrRecQ is positioned in a different orientation from that of the E. coli RecQ (EcRecQ). These results suggest that the orientation of the protein during DNA-binding is significantly different when comparing DrRecQ and EcRecQ.
    BioMed Research International 01/2014; 2014:342725. · 2.71 Impact Factor

Full-text

Download
2 Downloads
Available from