Hrq1, a homolog of the human RecQ4 helicase, acts catalytically and structurally to promote genome integrity

Matthew L. Bochman; Katrin Paeschke; Angela Chan; Virginia A. Zakian

doi:10.1016/j.celrep.2013.12.037

Hrq1, a homolog of the human RecQ4 helicase, acts catalytically and structurally to promote genome integrity

Matthew L. Bochman, Katrin Paeschke, Angela Chan, Virginia A. Zakian

Molecular Biology

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

Abstract

Human RecQ4 (hRecQ4) affects cancer and aging but is difficult to study because it is a fusion between a helicase and an essential replication factor. Budding yeast Hrq1 is homologous to the disease-linked helicase domain of RecQ4 and, like hRecQ4, is a robust 3'-5' helicase. Additionally, Hrq1 has the unusual property of forming heptameric rings. Cells lacking Hrq1 exhibited two DNA damage phenotypes: hypersensitivity to DNA interstrand crosslinks (ICLs) and telomere addition to DNA breaks. Both activities are rare; their coexistence in a single protein is unprecedented. Resistance to ICLs requires helicase activity, but suppression of telomere addition does not. Hrq1 also affects telomere length by a noncatalytic mechanism, as well as telomerase-independent telomere maintenance. Because Hrq1 binds telomeres invivo, it probably affects them directly. Thus, the tumor-suppressing activity of RecQ4 could be due to arole in ICL repair and/or suppression of de novo telomere addition.

Original language	English (US)
Pages (from-to)	346-356
Number of pages	11
Journal	Cell Reports
Volume	6
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2013.12.037
State	Published - 2014

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.celrep.2013.12.037

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title = "Hrq1, a homolog of the human RecQ4 helicase, acts catalytically and structurally to promote genome integrity",

abstract = "Human RecQ4 (hRecQ4) affects cancer and aging but is difficult to study because it is a fusion between a helicase and an essential replication factor. Budding yeast Hrq1 is homologous to the disease-linked helicase domain of RecQ4 and, like hRecQ4, is a robust 3'-5' helicase. Additionally, Hrq1 has the unusual property of forming heptameric rings. Cells lacking Hrq1 exhibited two DNA damage phenotypes: hypersensitivity to DNA interstrand crosslinks (ICLs) and telomere addition to DNA breaks. Both activities are rare; their coexistence in a single protein is unprecedented. Resistance to ICLs requires helicase activity, but suppression of telomere addition does not. Hrq1 also affects telomere length by a noncatalytic mechanism, as well as telomerase-independent telomere maintenance. Because Hrq1 binds telomeres invivo, it probably affects them directly. Thus, the tumor-suppressing activity of RecQ4 could be due to arole in ICL repair and/or suppression of de novo telomere addition.",

author = "Bochman, {Matthew L.} and Katrin Paeschke and Angela Chan and Zakian, {Virginia A.}",

note = "Funding Information: M.L.B. dedicates this article to the memory of Megan Davey who passed away during the course of this work. We thank Kathy Friedman, Margaret Platts, Kristina Schmidt, Raymund Wellinger, and Nadine Guenther for sharing their methods, suggesting experiments, for useful discussions, and assistance with experiments. Research in the Zakian laboratory is supported by grants from the National Institutes of Health (GM26938 and GM GM43265) and postdoctoral fellowships from the American Cancer Society (to M.L.B.; PF-10-145-01-DMC), the Deutsche Forschungsgemeinschaft (to K.P.), and the New Jersey Commission on Cancer Research (to K.P.). Research in the Paeschke laboratory is supported by the Emmy-Noether Program of the Deutsche Forschungsgemeinschaft. ",

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T1 - Hrq1, a homolog of the human RecQ4 helicase, acts catalytically and structurally to promote genome integrity

AU - Bochman, Matthew L.

AU - Paeschke, Katrin

AU - Chan, Angela

AU - Zakian, Virginia A.

N1 - Funding Information: M.L.B. dedicates this article to the memory of Megan Davey who passed away during the course of this work. We thank Kathy Friedman, Margaret Platts, Kristina Schmidt, Raymund Wellinger, and Nadine Guenther for sharing their methods, suggesting experiments, for useful discussions, and assistance with experiments. Research in the Zakian laboratory is supported by grants from the National Institutes of Health (GM26938 and GM GM43265) and postdoctoral fellowships from the American Cancer Society (to M.L.B.; PF-10-145-01-DMC), the Deutsche Forschungsgemeinschaft (to K.P.), and the New Jersey Commission on Cancer Research (to K.P.). Research in the Paeschke laboratory is supported by the Emmy-Noether Program of the Deutsche Forschungsgemeinschaft.

PY - 2014

Y1 - 2014

N2 - Human RecQ4 (hRecQ4) affects cancer and aging but is difficult to study because it is a fusion between a helicase and an essential replication factor. Budding yeast Hrq1 is homologous to the disease-linked helicase domain of RecQ4 and, like hRecQ4, is a robust 3'-5' helicase. Additionally, Hrq1 has the unusual property of forming heptameric rings. Cells lacking Hrq1 exhibited two DNA damage phenotypes: hypersensitivity to DNA interstrand crosslinks (ICLs) and telomere addition to DNA breaks. Both activities are rare; their coexistence in a single protein is unprecedented. Resistance to ICLs requires helicase activity, but suppression of telomere addition does not. Hrq1 also affects telomere length by a noncatalytic mechanism, as well as telomerase-independent telomere maintenance. Because Hrq1 binds telomeres invivo, it probably affects them directly. Thus, the tumor-suppressing activity of RecQ4 could be due to arole in ICL repair and/or suppression of de novo telomere addition.

AB - Human RecQ4 (hRecQ4) affects cancer and aging but is difficult to study because it is a fusion between a helicase and an essential replication factor. Budding yeast Hrq1 is homologous to the disease-linked helicase domain of RecQ4 and, like hRecQ4, is a robust 3'-5' helicase. Additionally, Hrq1 has the unusual property of forming heptameric rings. Cells lacking Hrq1 exhibited two DNA damage phenotypes: hypersensitivity to DNA interstrand crosslinks (ICLs) and telomere addition to DNA breaks. Both activities are rare; their coexistence in a single protein is unprecedented. Resistance to ICLs requires helicase activity, but suppression of telomere addition does not. Hrq1 also affects telomere length by a noncatalytic mechanism, as well as telomerase-independent telomere maintenance. Because Hrq1 binds telomeres invivo, it probably affects them directly. Thus, the tumor-suppressing activity of RecQ4 could be due to arole in ICL repair and/or suppression of de novo telomere addition.

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Hrq1, a homolog of the human RecQ4 helicase, acts catalytically and structurally to promote genome integrity

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