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Prelamin A impairs 53BP1 nuclear entry by mislocalizing NUP153 and disrupting the Ran gradient

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Prelamin A impairs 53BP1 nuclear entry by mislocalizing NUP153 and disrupting the Ran gradient. / Cobb, Andrew M.; Larrieu, Delphine; Warren, Derek T.; Liu, Yiwen; Srivastava, Sonal; Smith, Andrew J O; Bowater, Richard P.; Jackson, Stephen P.; Shanahan, Catherine M.

In: AGING CELL, Vol. 15, No. 6, 01.12.2016, p. 1039-1050.

Research output: Contribution to journalArticle

Harvard

Cobb, AM, Larrieu, D, Warren, DT, Liu, Y, Srivastava, S, Smith, AJO, Bowater, RP, Jackson, SP & Shanahan, CM 2016, 'Prelamin A impairs 53BP1 nuclear entry by mislocalizing NUP153 and disrupting the Ran gradient', AGING CELL, vol. 15, no. 6, pp. 1039-1050. https://doi.org/10.1111/acel.12506

APA

Cobb, A. M., Larrieu, D., Warren, D. T., Liu, Y., Srivastava, S., Smith, A. J. O., ... Shanahan, C. M. (2016). Prelamin A impairs 53BP1 nuclear entry by mislocalizing NUP153 and disrupting the Ran gradient. AGING CELL, 15(6), 1039-1050. https://doi.org/10.1111/acel.12506

Vancouver

Cobb AM, Larrieu D, Warren DT, Liu Y, Srivastava S, Smith AJO et al. Prelamin A impairs 53BP1 nuclear entry by mislocalizing NUP153 and disrupting the Ran gradient. AGING CELL. 2016 Dec 1;15(6):1039-1050. https://doi.org/10.1111/acel.12506

Author

Cobb, Andrew M. ; Larrieu, Delphine ; Warren, Derek T. ; Liu, Yiwen ; Srivastava, Sonal ; Smith, Andrew J O ; Bowater, Richard P. ; Jackson, Stephen P. ; Shanahan, Catherine M. / Prelamin A impairs 53BP1 nuclear entry by mislocalizing NUP153 and disrupting the Ran gradient. In: AGING CELL. 2016 ; Vol. 15, No. 6. pp. 1039-1050.

Bibtex Download

@article{393ebf89cca74d6285d669462157fc72,
title = "Prelamin A impairs 53BP1 nuclear entry by mislocalizing NUP153 and disrupting the Ran gradient",
abstract = "The nuclear lamina is essential for the proper structure and organization of the nucleus. Deregulation of A-type lamins can compromise genomic stability, alter chromatin organization and cause premature vascular aging. Here, we show that accumulation of the lamin A precursor, prelamin A, inhibits 53BP1 recruitment to sites of DNA damage and increases basal levels of DNA damage in aged vascular smooth muscle cells. We identify that this genome instability arises through defective nuclear import of 53BP1 as a consequence of abnormal topological arrangement of nucleoporin NUP153. We show for the first time that this nucleoporin is important for the nuclear localization of Ran and that the deregulated Ran gradient is likely to be compromising the nuclear import of 53BP1. Importantly, many of the defects associated with prelamin A expression were significantly reduced upon treatment with Remodelin, a small molecule recently reported to reverse deficiencies associated with abnormal nuclear lamina.",
keywords = "53BP1, cytoplasmic–nuclear trafficking, NUP153, prelamin A, Ran gradient, vascular disease",
author = "Cobb, {Andrew M.} and Delphine Larrieu and Warren, {Derek T.} and Yiwen Liu and Sonal Srivastava and Smith, {Andrew J O} and Bowater, {Richard P.} and Jackson, {Stephen P.} and Shanahan, {Catherine M.}",
year = "2016",
month = "12",
day = "1",
doi = "10.1111/acel.12506",
language = "English",
volume = "15",
pages = "1039--1050",
journal = "AGING CELL",
issn = "1474-9718",
publisher = "Wiley-Blackwell",
number = "6",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Prelamin A impairs 53BP1 nuclear entry by mislocalizing NUP153 and disrupting the Ran gradient

AU - Cobb, Andrew M.

AU - Larrieu, Delphine

AU - Warren, Derek T.

AU - Liu, Yiwen

AU - Srivastava, Sonal

AU - Smith, Andrew J O

AU - Bowater, Richard P.

AU - Jackson, Stephen P.

AU - Shanahan, Catherine M.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - The nuclear lamina is essential for the proper structure and organization of the nucleus. Deregulation of A-type lamins can compromise genomic stability, alter chromatin organization and cause premature vascular aging. Here, we show that accumulation of the lamin A precursor, prelamin A, inhibits 53BP1 recruitment to sites of DNA damage and increases basal levels of DNA damage in aged vascular smooth muscle cells. We identify that this genome instability arises through defective nuclear import of 53BP1 as a consequence of abnormal topological arrangement of nucleoporin NUP153. We show for the first time that this nucleoporin is important for the nuclear localization of Ran and that the deregulated Ran gradient is likely to be compromising the nuclear import of 53BP1. Importantly, many of the defects associated with prelamin A expression were significantly reduced upon treatment with Remodelin, a small molecule recently reported to reverse deficiencies associated with abnormal nuclear lamina.

AB - The nuclear lamina is essential for the proper structure and organization of the nucleus. Deregulation of A-type lamins can compromise genomic stability, alter chromatin organization and cause premature vascular aging. Here, we show that accumulation of the lamin A precursor, prelamin A, inhibits 53BP1 recruitment to sites of DNA damage and increases basal levels of DNA damage in aged vascular smooth muscle cells. We identify that this genome instability arises through defective nuclear import of 53BP1 as a consequence of abnormal topological arrangement of nucleoporin NUP153. We show for the first time that this nucleoporin is important for the nuclear localization of Ran and that the deregulated Ran gradient is likely to be compromising the nuclear import of 53BP1. Importantly, many of the defects associated with prelamin A expression were significantly reduced upon treatment with Remodelin, a small molecule recently reported to reverse deficiencies associated with abnormal nuclear lamina.

KW - 53BP1

KW - cytoplasmic–nuclear trafficking

KW - NUP153

KW - prelamin A

KW - Ran gradient

KW - vascular disease

UR - http://www.scopus.com/inward/record.url?scp=84979776450&partnerID=8YFLogxK

U2 - 10.1111/acel.12506

DO - 10.1111/acel.12506

M3 - Article

AN - SCOPUS:84979776450

VL - 15

SP - 1039

EP - 1050

JO - AGING CELL

JF - AGING CELL

SN - 1474-9718

IS - 6

ER -

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