14-3-3 checkpoint regulatory proteins interact specifically with DNA repair protein human exonuclease 1 (hEXO1) via a semi-conserved motif

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

14-3-3 checkpoint regulatory proteins interact specifically with DNA repair protein human exonuclease 1 (hEXO1) via a semi-conserved motif. / Andersen, Sofie Dabros; Keijzers, Guido; Rampakakis, Emmanouil; Engels, Kim; Luhn, Patricia; El-Shemerly, Mahmoud; Nielsen, Finn Cilius; Du, Yuhong; May, Alfred; Bohr, Vilhelm A; Ferrari, Stefano; Zannis-Hadjopoulos, Maria; Fu, Haian; Rasmussen, Lene Juel.

In: D N A Repair, Vol. 11, No. 3, 03.2012, p. 267-77.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Andersen, SD, Keijzers, G, Rampakakis, E, Engels, K, Luhn, P, El-Shemerly, M, Nielsen, FC, Du, Y, May, A, Bohr, VA, Ferrari, S, Zannis-Hadjopoulos, M, Fu, H & Rasmussen, LJ 2012, '14-3-3 checkpoint regulatory proteins interact specifically with DNA repair protein human exonuclease 1 (hEXO1) via a semi-conserved motif', D N A Repair, vol. 11, no. 3, pp. 267-77. https://doi.org/10.1016/j.dnarep.2011.11.007

APA

Andersen, S. D., Keijzers, G., Rampakakis, E., Engels, K., Luhn, P., El-Shemerly, M., ... Rasmussen, L. J. (2012). 14-3-3 checkpoint regulatory proteins interact specifically with DNA repair protein human exonuclease 1 (hEXO1) via a semi-conserved motif. D N A Repair, 11(3), 267-77. https://doi.org/10.1016/j.dnarep.2011.11.007

Vancouver

Andersen SD, Keijzers G, Rampakakis E, Engels K, Luhn P, El-Shemerly M et al. 14-3-3 checkpoint regulatory proteins interact specifically with DNA repair protein human exonuclease 1 (hEXO1) via a semi-conserved motif. D N A Repair. 2012 Mar;11(3):267-77. https://doi.org/10.1016/j.dnarep.2011.11.007

Author

Andersen, Sofie Dabros ; Keijzers, Guido ; Rampakakis, Emmanouil ; Engels, Kim ; Luhn, Patricia ; El-Shemerly, Mahmoud ; Nielsen, Finn Cilius ; Du, Yuhong ; May, Alfred ; Bohr, Vilhelm A ; Ferrari, Stefano ; Zannis-Hadjopoulos, Maria ; Fu, Haian ; Rasmussen, Lene Juel. / 14-3-3 checkpoint regulatory proteins interact specifically with DNA repair protein human exonuclease 1 (hEXO1) via a semi-conserved motif. In: D N A Repair. 2012 ; Vol. 11, No. 3. pp. 267-77.

Bibtex

@article{b96763cbf50c45839b38c32f426c8109,
title = "14-3-3 checkpoint regulatory proteins interact specifically with DNA repair protein human exonuclease 1 (hEXO1) via a semi-conserved motif",
abstract = "Human exonuclease 1 (hEXO1) acts directly in diverse DNA processing events, including replication, mismatch repair (MMR), and double strand break repair (DSBR), and it was also recently described to function as damage sensor and apoptosis inducer following DNA damage. In contrast, 14-3-3 proteins are regulatory phosphorserine/threonine binding proteins involved in the control of diverse cellular events, including cell cycle checkpoint and apoptosis signaling. hEXO1 is regulated by post-translation Ser/Thr phosphorylation in a yet not fully clarified manner, but evidently three phosphorylation sites are specifically induced by replication inhibition leading to protein ubiquitination and degradation. We demonstrate direct and robust interaction between hEXO1 and six of the seven 14-3-3 isoforms in vitro, suggestive of a novel protein interaction network between DNA repair and cell cycle control. Binding experiments reveal weak affinity of the more selective isoform 14-3-3s but both 14-3-3 isoforms ¿ and s significantly stimulate hEXO1 activity, indicating that these regulatory proteins exert a common regulation mode on hEXO1. Results demonstrate that binding involves the phosphorable amino acid S746 in hEXO1 and most likely a second unidentified binding motif. 14-3-3 associations do not appear to directly influence hEXO1 in vitro nuclease activity or in vitro DNA replication initiation. Moreover, specific phosphorylation variants, including hEXO1 S746A, are efficiently imported to the nucleus; to associate with PCNA in distinct replication foci and respond to DNA double strand breaks (DSBs), indicating that 14-3-3 binding does not involve regulating the subcellular distribution of hEXO1. Altogether, these results suggest that association may be related to regulation of hEXO1 availability during the DNA damage response to plausibly prevent extensive DNA resection at the damage site, as supported by recent studies.",
author = "Andersen, {Sofie Dabros} and Guido Keijzers and Emmanouil Rampakakis and Kim Engels and Patricia Luhn and Mahmoud El-Shemerly and Nielsen, {Finn Cilius} and Yuhong Du and Alfred May and Bohr, {Vilhelm A} and Stefano Ferrari and Maria Zannis-Hadjopoulos and Haian Fu and Rasmussen, {Lene Juel}",
note = "Copyright {\circledC} 2011 Elsevier B.V. All rights reserved.",
year = "2012",
month = "3",
doi = "10.1016/j.dnarep.2011.11.007",
language = "English",
volume = "11",
pages = "267--77",
journal = "D N A Repair",
issn = "1568-7864",
publisher = "Elsevier",
number = "3",

}

RIS

TY - JOUR

T1 - 14-3-3 checkpoint regulatory proteins interact specifically with DNA repair protein human exonuclease 1 (hEXO1) via a semi-conserved motif

AU - Andersen, Sofie Dabros

AU - Keijzers, Guido

AU - Rampakakis, Emmanouil

AU - Engels, Kim

AU - Luhn, Patricia

AU - El-Shemerly, Mahmoud

AU - Nielsen, Finn Cilius

AU - Du, Yuhong

AU - May, Alfred

AU - Bohr, Vilhelm A

AU - Ferrari, Stefano

AU - Zannis-Hadjopoulos, Maria

AU - Fu, Haian

AU - Rasmussen, Lene Juel

N1 - Copyright © 2011 Elsevier B.V. All rights reserved.

PY - 2012/3

Y1 - 2012/3

N2 - Human exonuclease 1 (hEXO1) acts directly in diverse DNA processing events, including replication, mismatch repair (MMR), and double strand break repair (DSBR), and it was also recently described to function as damage sensor and apoptosis inducer following DNA damage. In contrast, 14-3-3 proteins are regulatory phosphorserine/threonine binding proteins involved in the control of diverse cellular events, including cell cycle checkpoint and apoptosis signaling. hEXO1 is regulated by post-translation Ser/Thr phosphorylation in a yet not fully clarified manner, but evidently three phosphorylation sites are specifically induced by replication inhibition leading to protein ubiquitination and degradation. We demonstrate direct and robust interaction between hEXO1 and six of the seven 14-3-3 isoforms in vitro, suggestive of a novel protein interaction network between DNA repair and cell cycle control. Binding experiments reveal weak affinity of the more selective isoform 14-3-3s but both 14-3-3 isoforms ¿ and s significantly stimulate hEXO1 activity, indicating that these regulatory proteins exert a common regulation mode on hEXO1. Results demonstrate that binding involves the phosphorable amino acid S746 in hEXO1 and most likely a second unidentified binding motif. 14-3-3 associations do not appear to directly influence hEXO1 in vitro nuclease activity or in vitro DNA replication initiation. Moreover, specific phosphorylation variants, including hEXO1 S746A, are efficiently imported to the nucleus; to associate with PCNA in distinct replication foci and respond to DNA double strand breaks (DSBs), indicating that 14-3-3 binding does not involve regulating the subcellular distribution of hEXO1. Altogether, these results suggest that association may be related to regulation of hEXO1 availability during the DNA damage response to plausibly prevent extensive DNA resection at the damage site, as supported by recent studies.

AB - Human exonuclease 1 (hEXO1) acts directly in diverse DNA processing events, including replication, mismatch repair (MMR), and double strand break repair (DSBR), and it was also recently described to function as damage sensor and apoptosis inducer following DNA damage. In contrast, 14-3-3 proteins are regulatory phosphorserine/threonine binding proteins involved in the control of diverse cellular events, including cell cycle checkpoint and apoptosis signaling. hEXO1 is regulated by post-translation Ser/Thr phosphorylation in a yet not fully clarified manner, but evidently three phosphorylation sites are specifically induced by replication inhibition leading to protein ubiquitination and degradation. We demonstrate direct and robust interaction between hEXO1 and six of the seven 14-3-3 isoforms in vitro, suggestive of a novel protein interaction network between DNA repair and cell cycle control. Binding experiments reveal weak affinity of the more selective isoform 14-3-3s but both 14-3-3 isoforms ¿ and s significantly stimulate hEXO1 activity, indicating that these regulatory proteins exert a common regulation mode on hEXO1. Results demonstrate that binding involves the phosphorable amino acid S746 in hEXO1 and most likely a second unidentified binding motif. 14-3-3 associations do not appear to directly influence hEXO1 in vitro nuclease activity or in vitro DNA replication initiation. Moreover, specific phosphorylation variants, including hEXO1 S746A, are efficiently imported to the nucleus; to associate with PCNA in distinct replication foci and respond to DNA double strand breaks (DSBs), indicating that 14-3-3 binding does not involve regulating the subcellular distribution of hEXO1. Altogether, these results suggest that association may be related to regulation of hEXO1 availability during the DNA damage response to plausibly prevent extensive DNA resection at the damage site, as supported by recent studies.

U2 - 10.1016/j.dnarep.2011.11.007

DO - 10.1016/j.dnarep.2011.11.007

M3 - Journal article

VL - 11

SP - 267

EP - 277

JO - D N A Repair

JF - D N A Repair

SN - 1568-7864

IS - 3

ER -

ID: 38379185