Dual DNA unwinding activities of the Rothmund-Thomson syndrome protein, RECQ4.

Abstract

Human RECQ helicases have been linked to distinct clinical diseases with increased cancer rates and premature ageing. All RECQ proteins, except RECQ4, have been shown to be functional helicases. Mutations in RECQ4 lead to Rothmund-Thomson syndrome (RTS), and mouse models reveal that the conserved helicase motifs are required for avoidance of RTS. Furthermore, the amino (N) terminus of RECQ4 shares homology with yeast DNA replication initiation factor, Sld2, and is vital for embryonic development. Here, in contrast to previous reports, we show that RECQ4 exhibits DNA helicase activity. Importantly, two distinct regions of the protein, the conserved helicase motifs and the Sld2-like N-terminal domain, each independently promote ATP-dependent DNA unwinding. Taken together, our data provide the first biochemical clues underlying the molecular function of RECQ4 in DNA replication and genome maintenance.

• Authors: Xiaohua Xu, Yilun Liu
• Journal: The EMBO journal (EMBO J) Vol. 28 Issue 5 Pg. 568-77 (Mar 04 2009) ISSN: 1460-2075 [Electronic] England
• PMID: 19177149 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Cycle Proteins
• Recombinant Proteins
• SLD2 protein, S cerevisiae
• Saccharomyces cerevisiae Proteins
• Adenosine Triphosphate
• RECQL4 protein, human
• RecQ Helicases

Topics

• Adenosine Triphosphate (metabolism)
• Cell Cycle Proteins (genetics)
• DNA Replication
• Humans
• Mutation
• Protein Structure, Tertiary
• RecQ Helicases (chemistry, genetics, physiology)
• Recombinant Proteins (chemistry, genetics)
• Rothmund-Thomson Syndrome (genetics)
• Saccharomyces cerevisiae Proteins (genetics)