The helicase and ATPase activities of RECQL4 are compromised by mutations reported in three human patients

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The helicase and ATPase activities of RECQL4 are compromised by mutations reported in three human patients. / Jensen, Martin Borch; Dunn, Christopher A; Keijzers, Guido; Kulikowicz, Tomasz; Rasmussen, Lene Juel; Croteau, Deborah L; Bohr, Vilhelm A.

In: Aging, Vol. 4, No. 11, 11.2012, p. 790-802.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Jensen, MB, Dunn, CA, Keijzers, G, Kulikowicz, T, Rasmussen, LJ, Croteau, DL & Bohr, VA 2012, 'The helicase and ATPase activities of RECQL4 are compromised by mutations reported in three human patients', Aging, vol. 4, no. 11, pp. 790-802.

APA

Jensen, M. B., Dunn, C. A., Keijzers, G., Kulikowicz, T., Rasmussen, L. J., Croteau, D. L., & Bohr, V. A. (2012). The helicase and ATPase activities of RECQL4 are compromised by mutations reported in three human patients. Aging, 4(11), 790-802.

Vancouver

Jensen MB, Dunn CA, Keijzers G, Kulikowicz T, Rasmussen LJ, Croteau DL et al. The helicase and ATPase activities of RECQL4 are compromised by mutations reported in three human patients. Aging. 2012 Nov;4(11):790-802.

Author

Jensen, Martin Borch ; Dunn, Christopher A ; Keijzers, Guido ; Kulikowicz, Tomasz ; Rasmussen, Lene Juel ; Croteau, Deborah L ; Bohr, Vilhelm A. / The helicase and ATPase activities of RECQL4 are compromised by mutations reported in three human patients. In: Aging. 2012 ; Vol. 4, No. 11. pp. 790-802.

Bibtex

@article{a419e52e384a40e18309b8e4e0993cc5,
title = "The helicase and ATPase activities of RECQL4 are compromised by mutations reported in three human patients",
abstract = "RECQL4 is one of five members of the human RecQ helicase family, and is implicated in three syndromes displaying accelerating aging, developmental abnormalities and a predisposition to cancer. In this study, we purified three variants of RECQL4 carrying previously reported patient mutations. These three mutant proteins were analyzed for the known biochemical activities of RECQL4: DNA binding, unwinding of duplex DNA, ATP hydrolysis and annealing of simplex DNA. Further, the mutant proteins were evaluated for stability and recruitment to sites of laser-induced DNA damage. One mutant was helicase-dead, had marginal ATPase activity and may be structurally compromised, while the other two showed greatly reduced helicase and ATPase activities. The remaining biochemical activities and ability to recruit to damage sites were not significantly impaired for any of the mutants. Our findings demonstrate a consistent pattern of functional deficiency and provide further support for a helicase-dependent cellular function of RECQL4 in addition to its N-terminus-dependent role in initiation of replication, a function that may underlie the phenotype of RECQL4-linked disease.",
author = "Jensen, {Martin Borch} and Dunn, {Christopher A} and Guido Keijzers and Tomasz Kulikowicz and Rasmussen, {Lene Juel} and Croteau, {Deborah L} and Bohr, {Vilhelm A}",
year = "2012",
month = "11",
language = "English",
volume = "4",
pages = "790--802",
journal = "Aging",
issn = "1945-4589",
publisher = "Impact Journals LLC",
number = "11",

}

RIS

TY - JOUR

T1 - The helicase and ATPase activities of RECQL4 are compromised by mutations reported in three human patients

AU - Jensen, Martin Borch

AU - Dunn, Christopher A

AU - Keijzers, Guido

AU - Kulikowicz, Tomasz

AU - Rasmussen, Lene Juel

AU - Croteau, Deborah L

AU - Bohr, Vilhelm A

PY - 2012/11

Y1 - 2012/11

N2 - RECQL4 is one of five members of the human RecQ helicase family, and is implicated in three syndromes displaying accelerating aging, developmental abnormalities and a predisposition to cancer. In this study, we purified three variants of RECQL4 carrying previously reported patient mutations. These three mutant proteins were analyzed for the known biochemical activities of RECQL4: DNA binding, unwinding of duplex DNA, ATP hydrolysis and annealing of simplex DNA. Further, the mutant proteins were evaluated for stability and recruitment to sites of laser-induced DNA damage. One mutant was helicase-dead, had marginal ATPase activity and may be structurally compromised, while the other two showed greatly reduced helicase and ATPase activities. The remaining biochemical activities and ability to recruit to damage sites were not significantly impaired for any of the mutants. Our findings demonstrate a consistent pattern of functional deficiency and provide further support for a helicase-dependent cellular function of RECQL4 in addition to its N-terminus-dependent role in initiation of replication, a function that may underlie the phenotype of RECQL4-linked disease.

AB - RECQL4 is one of five members of the human RecQ helicase family, and is implicated in three syndromes displaying accelerating aging, developmental abnormalities and a predisposition to cancer. In this study, we purified three variants of RECQL4 carrying previously reported patient mutations. These three mutant proteins were analyzed for the known biochemical activities of RECQL4: DNA binding, unwinding of duplex DNA, ATP hydrolysis and annealing of simplex DNA. Further, the mutant proteins were evaluated for stability and recruitment to sites of laser-induced DNA damage. One mutant was helicase-dead, had marginal ATPase activity and may be structurally compromised, while the other two showed greatly reduced helicase and ATPase activities. The remaining biochemical activities and ability to recruit to damage sites were not significantly impaired for any of the mutants. Our findings demonstrate a consistent pattern of functional deficiency and provide further support for a helicase-dependent cellular function of RECQL4 in addition to its N-terminus-dependent role in initiation of replication, a function that may underlie the phenotype of RECQL4-linked disease.

M3 - Journal article

VL - 4

SP - 790

EP - 802

JO - Aging

JF - Aging

SN - 1945-4589

IS - 11

ER -

ID: 44690230