Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage-modified chromatin

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Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage-modified chromatin. / Melander, Fredrik; Bekker-Jensen, Simon; Falck, Jacob; Bartek, Jiri; Mailand, Niels; Lukas, Jiri.

In: Journal of Cell Biology, Vol. 181, No. 2, 21.04.2008, p. 213-26.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Melander, F, Bekker-Jensen, S, Falck, J, Bartek, J, Mailand, N & Lukas, J 2008, 'Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage-modified chromatin', Journal of Cell Biology, vol. 181, no. 2, pp. 213-26. https://doi.org/10.1083/jcb.200708210

APA

Melander, F., Bekker-Jensen, S., Falck, J., Bartek, J., Mailand, N., & Lukas, J. (2008). Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage-modified chromatin. Journal of Cell Biology, 181(2), 213-26. https://doi.org/10.1083/jcb.200708210

Vancouver

Melander F, Bekker-Jensen S, Falck J, Bartek J, Mailand N, Lukas J. Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage-modified chromatin. Journal of Cell Biology. 2008 Apr 21;181(2):213-26. https://doi.org/10.1083/jcb.200708210

Author

Melander, Fredrik ; Bekker-Jensen, Simon ; Falck, Jacob ; Bartek, Jiri ; Mailand, Niels ; Lukas, Jiri. / Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage-modified chromatin. In: Journal of Cell Biology. 2008 ; Vol. 181, No. 2. pp. 213-26.

Bibtex

@article{2d03063a0da148e19586b4d76c4a3f59,
title = "Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage-modified chromatin",
abstract = "DNA double-strand breaks (DSBs) trigger accumulation of the MRE11-RAD50-Nijmegen breakage syndrome 1 (NBS1 [MRN]) complex, whose retention on the DSB-flanking chromatin facilitates survival. Chromatin retention of MRN requires the MDC1 adaptor protein, but the mechanism behind the MRN-MDC1 interaction is unknown. We show that the NBS1 subunit of MRN interacts with the MDC1 N terminus enriched in Ser-Asp-Thr (SDT) repeats. This interaction was constitutive and mediated by binding between the phosphorylated SDT repeats of MDC1 and the phosphate-binding forkhead-associated domain of NBS1. Phosphorylation of the SDT repeats by casein kinase 2 (CK2) was sufficient to trigger MDC1-NBS1 interaction in vitro, and MDC1 associated with CK2 activity in cells. Inhibition of CK2 reduced SDT phosphorylation in vivo, and disruption of the SDT-associated phosphoacceptor sites prevented the retention of NBS1 at DSBs. Together, these data suggest that phosphorylation of the SDT repeats in the MDC1 N terminus functions to recruit NBS1 and, thereby, increases the local concentration of MRN at the sites of chromosomal breakage.",
author = "Fredrik Melander and Simon Bekker-Jensen and Jacob Falck and Jiri Bartek and Niels Mailand and Jiri Lukas",
year = "2008",
month = apr,
day = "21",
doi = "10.1083/jcb.200708210",
language = "English",
volume = "181",
pages = "213--26",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "2",

}

RIS

TY - JOUR

T1 - Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage-modified chromatin

AU - Melander, Fredrik

AU - Bekker-Jensen, Simon

AU - Falck, Jacob

AU - Bartek, Jiri

AU - Mailand, Niels

AU - Lukas, Jiri

PY - 2008/4/21

Y1 - 2008/4/21

N2 - DNA double-strand breaks (DSBs) trigger accumulation of the MRE11-RAD50-Nijmegen breakage syndrome 1 (NBS1 [MRN]) complex, whose retention on the DSB-flanking chromatin facilitates survival. Chromatin retention of MRN requires the MDC1 adaptor protein, but the mechanism behind the MRN-MDC1 interaction is unknown. We show that the NBS1 subunit of MRN interacts with the MDC1 N terminus enriched in Ser-Asp-Thr (SDT) repeats. This interaction was constitutive and mediated by binding between the phosphorylated SDT repeats of MDC1 and the phosphate-binding forkhead-associated domain of NBS1. Phosphorylation of the SDT repeats by casein kinase 2 (CK2) was sufficient to trigger MDC1-NBS1 interaction in vitro, and MDC1 associated with CK2 activity in cells. Inhibition of CK2 reduced SDT phosphorylation in vivo, and disruption of the SDT-associated phosphoacceptor sites prevented the retention of NBS1 at DSBs. Together, these data suggest that phosphorylation of the SDT repeats in the MDC1 N terminus functions to recruit NBS1 and, thereby, increases the local concentration of MRN at the sites of chromosomal breakage.

AB - DNA double-strand breaks (DSBs) trigger accumulation of the MRE11-RAD50-Nijmegen breakage syndrome 1 (NBS1 [MRN]) complex, whose retention on the DSB-flanking chromatin facilitates survival. Chromatin retention of MRN requires the MDC1 adaptor protein, but the mechanism behind the MRN-MDC1 interaction is unknown. We show that the NBS1 subunit of MRN interacts with the MDC1 N terminus enriched in Ser-Asp-Thr (SDT) repeats. This interaction was constitutive and mediated by binding between the phosphorylated SDT repeats of MDC1 and the phosphate-binding forkhead-associated domain of NBS1. Phosphorylation of the SDT repeats by casein kinase 2 (CK2) was sufficient to trigger MDC1-NBS1 interaction in vitro, and MDC1 associated with CK2 activity in cells. Inhibition of CK2 reduced SDT phosphorylation in vivo, and disruption of the SDT-associated phosphoacceptor sites prevented the retention of NBS1 at DSBs. Together, these data suggest that phosphorylation of the SDT repeats in the MDC1 N terminus functions to recruit NBS1 and, thereby, increases the local concentration of MRN at the sites of chromosomal breakage.

U2 - 10.1083/jcb.200708210

DO - 10.1083/jcb.200708210

M3 - Journal article

C2 - 18411307

VL - 181

SP - 213

EP - 226

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 2

ER -

ID: 35306104