Acute MUS81 depletion leads to replication fork slowing and a constitutive DNA damage response

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

Standard

Acute MUS81 depletion leads to replication fork slowing and a constitutive DNA damage response. / Xing, Meichun; Wang, Xiaohui; Palmai-Pallag, Timea; Shen, Huahao; Helleday, Thomas; Hickson, Ian D.; Ying, Songmin.

In: OncoTarget, Vol. 6, No. 35, 2015, p. 37638-37646.

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

Harvard

Xing, M, Wang, X, Palmai-Pallag, T, Shen, H, Helleday, T, Hickson, ID & Ying, S 2015, 'Acute MUS81 depletion leads to replication fork slowing and a constitutive DNA damage response', OncoTarget, vol. 6, no. 35, pp. 37638-37646. <http://10.18632/oncotarget.5497>

APA

Xing, M., Wang, X., Palmai-Pallag, T., Shen, H., Helleday, T., Hickson, I. D., & Ying, S. (2015). Acute MUS81 depletion leads to replication fork slowing and a constitutive DNA damage response. OncoTarget, 6(35), 37638-37646. http://10.18632/oncotarget.5497

Vancouver

Xing M, Wang X, Palmai-Pallag T, Shen H, Helleday T, Hickson ID et al. Acute MUS81 depletion leads to replication fork slowing and a constitutive DNA damage response. OncoTarget. 2015;6(35):37638-37646.

Author

Xing, Meichun ; Wang, Xiaohui ; Palmai-Pallag, Timea ; Shen, Huahao ; Helleday, Thomas ; Hickson, Ian D. ; Ying, Songmin. / Acute MUS81 depletion leads to replication fork slowing and a constitutive DNA damage response. In: OncoTarget. 2015 ; Vol. 6, No. 35. pp. 37638-37646.

Bibtex

@article{7d91fa1e35f04bb5bec53f40b41c0753,
title = "Acute MUS81 depletion leads to replication fork slowing and a constitutive DNA damage response",
abstract = "The MUS81 protein belongs to a conserved family of DNA structure-specific nucleases that play important roles in DNA replication and repair. Inactivation of the Mus81 gene in mice has no major deleterious consequences for embryonic development, although cancer susceptibility has been reported. We have investigated the role of MUS81 in human cells by acutely depleting the protein using shRNAs. We found that MUS81 depletion from human fibroblasts leads to accumulation of ssDNA and a constitutive DNA damage response that ultimately activates cellular senescence. Moreover, we show that MUS81 is required for efficient replication fork progression during an unperturbed S-phase, and for recovery of productive replication following replication stalling. These results demonstrate essential roles for the MUS81 nuclease in maintenance of replication fork integrity.",
keywords = "cellular senescence, DNA replication, Holliday junctions, homologous recombination, NBS1",
author = "Meichun Xing and Xiaohui Wang and Timea Palmai-Pallag and Huahao Shen and Thomas Helleday and Hickson, {Ian D.} and Songmin Ying",
year = "2015",
language = "English",
volume = "6",
pages = "37638--37646",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "35",

}

RIS

TY - JOUR

T1 - Acute MUS81 depletion leads to replication fork slowing and a constitutive DNA damage response

AU - Xing, Meichun

AU - Wang, Xiaohui

AU - Palmai-Pallag, Timea

AU - Shen, Huahao

AU - Helleday, Thomas

AU - Hickson, Ian D.

AU - Ying, Songmin

PY - 2015

Y1 - 2015

N2 - The MUS81 protein belongs to a conserved family of DNA structure-specific nucleases that play important roles in DNA replication and repair. Inactivation of the Mus81 gene in mice has no major deleterious consequences for embryonic development, although cancer susceptibility has been reported. We have investigated the role of MUS81 in human cells by acutely depleting the protein using shRNAs. We found that MUS81 depletion from human fibroblasts leads to accumulation of ssDNA and a constitutive DNA damage response that ultimately activates cellular senescence. Moreover, we show that MUS81 is required for efficient replication fork progression during an unperturbed S-phase, and for recovery of productive replication following replication stalling. These results demonstrate essential roles for the MUS81 nuclease in maintenance of replication fork integrity.

AB - The MUS81 protein belongs to a conserved family of DNA structure-specific nucleases that play important roles in DNA replication and repair. Inactivation of the Mus81 gene in mice has no major deleterious consequences for embryonic development, although cancer susceptibility has been reported. We have investigated the role of MUS81 in human cells by acutely depleting the protein using shRNAs. We found that MUS81 depletion from human fibroblasts leads to accumulation of ssDNA and a constitutive DNA damage response that ultimately activates cellular senescence. Moreover, we show that MUS81 is required for efficient replication fork progression during an unperturbed S-phase, and for recovery of productive replication following replication stalling. These results demonstrate essential roles for the MUS81 nuclease in maintenance of replication fork integrity.

KW - cellular senescence

KW - DNA replication

KW - Holliday junctions

KW - homologous recombination

KW - NBS1

M3 - Journal article

VL - 6

SP - 37638

EP - 37646

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 35

ER -

ID: 160899134