hSSB1 phosphorylation is dynamically regulated by DNA-PK and PPP-family protein phosphatases

Nicholas W. Ashton; Nicolas Paquet; Sally L. Shirran; Emma Bolderson; Ruvini Kariawasam; Christine Touma; Azadeh Fallahbaghery; Roland Gamsjaeger; Liza Cubeddu; Catherine Botting; Pamela M. Pollock; Kenneth J. O’Byrne; Derek J. Richard

doi:10.1016/j.dnarep.2017.03.006

hSSB1 phosphorylation is dynamically regulated by DNA-PK and PPP-family protein phosphatases

Nicholas W. Ashton, Nicolas Paquet, Sally L. Shirran, Emma Bolderson, Ruvini Kariawasam, Christine Touma, Azadeh Fallahbaghery, Roland Gamsjaeger, Liza Cubeddu, Catherine Botting, Pamela M. Pollock, Kenneth J. O’Byrne, Derek J. Richard

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

Abstract

The maintenance of genomic stability is essential for cellular viability and the prevention of diseases such as cancer. Human single-stranded DNA-binding protein 1 (hSSB1) is a protein with roles in the stabilisation and restart of stalled DNA replication forks, as well as in the repair of oxidative DNA lesions and double-strand DNA breaks. In the latter process, phosphorylation of threonine 117 by the ATM kinase is required for hSSB1 stability and efficient DNA repair. The regulation of hSSB1 in other DNA repair pathways has however remained unclear. Here we report that hSSB1 is also directly phosphorylated by DNA-PK at serine residue 134. While this modification is largely suppressed in undamaged cells by PPP-family protein phosphatases, S134 phosphorylation is enhanced following the disruption of replication forks and promotes cellular survival. Together, these data thereby represent a novel mechanism for hSSB1 regulation following the inhibition of replication.

Original language	English
Pages (from-to)	30-39
Number of pages	10
Journal	DNA Repair
Volume	54
Early online date	6 Apr 2017
DOIs	https://doi.org/10.1016/j.dnarep.2017.03.006
Publication status	Published - Jun 2017

Keywords

hSSB1
DNA-PK
PPP-Family Phosphatase
Replication Fork
Replication Stress

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.dnarep.2017.03.006Licence: CC BY

Shirran_2017_DNARepair_hSSB1_CC
© 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).
Final published version, 1.11 MBLicence: CC BY

Cite this

@article{fdbe09722e2c41b28ad5cbebb2e54dde,

title = "hSSB1 phosphorylation is dynamically regulated by DNA-PK and PPP-family protein phosphatases",

abstract = "The maintenance of genomic stability is essential for cellular viability and the prevention of diseases such as cancer. Human single-stranded DNA-binding protein 1 (hSSB1) is a protein with roles in the stabilisation and restart of stalled DNA replication forks, as well as in the repair of oxidative DNA lesions and double-strand DNA breaks. In the latter process, phosphorylation of threonine 117 by the ATM kinase is required for hSSB1 stability and efficient DNA repair. The regulation of hSSB1 in other DNA repair pathways has however remained unclear. Here we report that hSSB1 is also directly phosphorylated by DNA-PK at serine residue 134. While this modification is largely suppressed in undamaged cells by PPP-family protein phosphatases, S134 phosphorylation is enhanced following the disruption of replication forks and promotes cellular survival. Together, these data thereby represent a novel mechanism for hSSB1 regulation following the inhibition of replication.",

keywords = "hSSB1, DNA-PK, PPP-Family Phosphatase, Replication Fork, Replication Stress",

author = "Ashton, {Nicholas W.} and Nicolas Paquet and Shirran, {Sally L.} and Emma Bolderson and Ruvini Kariawasam and Christine Touma and Azadeh Fallahbaghery and Roland Gamsjaeger and Liza Cubeddu and Catherine Botting and Pollock, {Pamela M.} and O{\textquoteright}Byrne, {Kenneth J.} and Richard, {Derek J.}",

note = "This work was supported by a National Health and Medical Research Council project grant [1066550], an Australian Research Council project grant [DP 120103099] and by a Queensland Health Senior Clinical Research Fellowship awarded to K.J.O. This work was also supported by the Wellcome Trust [094476/Z/10/Z], which funded the purchase of the TripleTOF 5600 mass spectrometer at the BSRC Mass Spectrometry and Proteomics Facility, University of St Andrews. NWA was supported by a scholarship awarded by Cancer Council Queensland. E.B. is supported by an Advance Queensland Research Fellowship. ",

year = "2017",

month = jun,

doi = "10.1016/j.dnarep.2017.03.006",

language = "English",

volume = "54",

pages = "30--39",

journal = "DNA Repair",

issn = "1568-7864",

publisher = "Elsevier",

}

TY - JOUR

T1 - hSSB1 phosphorylation is dynamically regulated by DNA-PK and PPP-family protein phosphatases

AU - Ashton, Nicholas W.

AU - Paquet, Nicolas

AU - Shirran, Sally L.

AU - Bolderson, Emma

AU - Kariawasam, Ruvini

AU - Touma, Christine

AU - Fallahbaghery, Azadeh

AU - Gamsjaeger, Roland

AU - Cubeddu, Liza

AU - Botting, Catherine

AU - Pollock, Pamela M.

AU - O’Byrne, Kenneth J.

AU - Richard, Derek J.

N1 - This work was supported by a National Health and Medical Research Council project grant [1066550], an Australian Research Council project grant [DP 120103099] and by a Queensland Health Senior Clinical Research Fellowship awarded to K.J.O. This work was also supported by the Wellcome Trust [094476/Z/10/Z], which funded the purchase of the TripleTOF 5600 mass spectrometer at the BSRC Mass Spectrometry and Proteomics Facility, University of St Andrews. NWA was supported by a scholarship awarded by Cancer Council Queensland. E.B. is supported by an Advance Queensland Research Fellowship.

PY - 2017/6

Y1 - 2017/6

N2 - The maintenance of genomic stability is essential for cellular viability and the prevention of diseases such as cancer. Human single-stranded DNA-binding protein 1 (hSSB1) is a protein with roles in the stabilisation and restart of stalled DNA replication forks, as well as in the repair of oxidative DNA lesions and double-strand DNA breaks. In the latter process, phosphorylation of threonine 117 by the ATM kinase is required for hSSB1 stability and efficient DNA repair. The regulation of hSSB1 in other DNA repair pathways has however remained unclear. Here we report that hSSB1 is also directly phosphorylated by DNA-PK at serine residue 134. While this modification is largely suppressed in undamaged cells by PPP-family protein phosphatases, S134 phosphorylation is enhanced following the disruption of replication forks and promotes cellular survival. Together, these data thereby represent a novel mechanism for hSSB1 regulation following the inhibition of replication.

AB - The maintenance of genomic stability is essential for cellular viability and the prevention of diseases such as cancer. Human single-stranded DNA-binding protein 1 (hSSB1) is a protein with roles in the stabilisation and restart of stalled DNA replication forks, as well as in the repair of oxidative DNA lesions and double-strand DNA breaks. In the latter process, phosphorylation of threonine 117 by the ATM kinase is required for hSSB1 stability and efficient DNA repair. The regulation of hSSB1 in other DNA repair pathways has however remained unclear. Here we report that hSSB1 is also directly phosphorylated by DNA-PK at serine residue 134. While this modification is largely suppressed in undamaged cells by PPP-family protein phosphatases, S134 phosphorylation is enhanced following the disruption of replication forks and promotes cellular survival. Together, these data thereby represent a novel mechanism for hSSB1 regulation following the inhibition of replication.

KW - hSSB1

KW - DNA-PK

KW - PPP-Family Phosphatase

KW - Replication Fork

KW - Replication Stress

UR - http://www.sciencedirect.com/science/article/pii/S1568786417300046#appd002

U2 - 10.1016/j.dnarep.2017.03.006

DO - 10.1016/j.dnarep.2017.03.006

M3 - Article

SN - 1568-7864

VL - 54

SP - 30

EP - 39

JO - DNA Repair

JF - DNA Repair

ER -

hSSB1 phosphorylation is dynamically regulated by DNA-PK and PPP-family protein phosphatases

Abstract

Keywords

UN SDGs

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hSSB1 phosphorylation is dynamically regulated by DNA-PK and PPP-family protein phosphatases

Abstract

Keywords

UN SDGs

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Other files and links

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MaXis ESI QTOF mass spectrometer: Equipment only grant-Mass spectrometers for Proteomics, Lipidomics and focused Metabolomics research

Cite this