Nature Structural and Molecular Biology, volume 27, issue 12, pages 1152-1164
Regulation of ALT-associated homology-directed repair by polyADP-ribosylation
Hoang Song-My
1
,
Kaminski Nicole
1
,
Bhargava Ragini
1
,
Barroso González Jonathan
1
,
Lynskey Michelle L
1
,
Garcia Exposito Laura
1
,
Roncaioli Justin L
1
,
Wondisford Anne R
1
,
Wallace Callen
2
,
Watkins Simon C.
2
,
James Dominic I.
3
,
WADDELL IAN D.
3
,
Ogilvie Donald
3
,
Smith Kate M.
3
,
Leprevost Felipe Da Veiga
4
,
Mellacheruvu Dattatreya
4
,
Nesvizhskii Alexey I.
4, 5
,
Li Jianfeng
6
,
Ray-Gallet Dominique
7
,
Sobol Robert E.
6
,
Almouzni Geneviève
7
,
Osullivan Roderick J
1
1
Department of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, USA
|
2
Department of Cell Biology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, USA
|
4
Department of Pathology, University of Michigan, Ann Arbor, USA
|
5
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, USA
|
6
Department of Pharmacology and the Mitchell Cancer Institute, University of South Alabama, Mobile, USA
|
Publication type: Journal Article
Publication date: 2020-10-12
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 16.8
ISSN: 15459993, 15459985
PubMed ID:
33046907
Molecular Biology
Structural Biology
Abstract
The synthesis of poly(ADP-ribose) (PAR) reconfigures the local chromatin environment and recruits DNA-repair complexes to damaged chromatin. PAR degradation by poly(ADP-ribose) glycohydrolase (PARG) is essential for progression and completion of DNA repair. Here, we show that inhibition of PARG disrupts homology-directed repair (HDR) mechanisms that underpin alternative lengthening of telomeres (ALT). Proteomic analyses uncover a new role for poly(ADP-ribosyl)ation (PARylation) in regulating the chromatin-assembly factor HIRA in ALT cancer cells. We show that HIRA is enriched at telomeres during the G2 phase and is required for histone H3.3 deposition and telomere DNA synthesis. Depletion of HIRA elicits systemic death of ALT cancer cells that is mitigated by re-expression of ATRX, a protein that is frequently inactivated in ALT tumors. We propose that PARylation enables HIRA to fulfill its essential role in the adaptive response to ATRX deficiency that pervades ALT cancers.
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Hoang S. et al. Regulation of ALT-associated homology-directed repair by polyADP-ribosylation // Nature Structural and Molecular Biology. 2020. Vol. 27. No. 12. pp. 1152-1164.
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Hoang S., Kaminski N., Bhargava R., Barroso González J., Lynskey M. L., Garcia Exposito L., Roncaioli J. L., Wondisford A. R., Wallace C., Watkins S. C., James D. I., WADDELL I. D., Ogilvie D., Smith K. M., Leprevost F. D. V., Mellacheruvu D., Nesvizhskii A. I., Li J., Ray-Gallet D., Sobol R. E., Almouzni G., Osullivan R. J. Regulation of ALT-associated homology-directed repair by polyADP-ribosylation // Nature Structural and Molecular Biology. 2020. Vol. 27. No. 12. pp. 1152-1164.
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TY - JOUR
DO - 10.1038/s41594-020-0512-7
UR - https://doi.org/10.1038%2Fs41594-020-0512-7
TI - Regulation of ALT-associated homology-directed repair by polyADP-ribosylation
T2 - Nature Structural and Molecular Biology
AU - Hoang, Song-My
AU - Kaminski, Nicole
AU - Bhargava, Ragini
AU - Barroso González, Jonathan
AU - Lynskey, Michelle L
AU - Garcia Exposito, Laura
AU - Roncaioli, Justin L
AU - Wondisford, Anne R
AU - Wallace, Callen
AU - Watkins, Simon C.
AU - James, Dominic I.
AU - WADDELL, IAN D.
AU - Ogilvie, Donald
AU - Smith, Kate M.
AU - Leprevost, Felipe Da Veiga
AU - Mellacheruvu, Dattatreya
AU - Nesvizhskii, Alexey I.
AU - Li, Jianfeng
AU - Ray-Gallet, Dominique
AU - Sobol, Robert E.
AU - Almouzni, Geneviève
AU - Osullivan, Roderick J
PY - 2020
DA - 2020/10/12 00:00:00
PB - Springer Nature
SP - 1152-1164
IS - 12
VL - 27
PMID - 33046907
SN - 1545-9993
SN - 1545-9985
ER -
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@article{2020_Hoang,
author = {Song-My Hoang and Nicole Kaminski and Ragini Bhargava and Jonathan Barroso González and Michelle L Lynskey and Laura Garcia Exposito and Justin L Roncaioli and Anne R Wondisford and Callen Wallace and Simon C. Watkins and Dominic I. James and IAN D. WADDELL and Donald Ogilvie and Kate M. Smith and Felipe Da Veiga Leprevost and Dattatreya Mellacheruvu and Alexey I. Nesvizhskii and Jianfeng Li and Dominique Ray-Gallet and Robert E. Sobol and Geneviève Almouzni and Roderick J Osullivan},
title = {Regulation of ALT-associated homology-directed repair by polyADP-ribosylation},
journal = {Nature Structural and Molecular Biology},
year = {2020},
volume = {27},
publisher = {Springer Nature},
month = {oct},
url = {https://doi.org/10.1038%2Fs41594-020-0512-7},
number = {12},
pages = {1152--1164},
doi = {10.1038/s41594-020-0512-7}
}
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Hoang, Song-My, et al. “Regulation of ALT-associated homology-directed repair by polyADP-ribosylation.” Nature Structural and Molecular Biology, vol. 27, no. 12, Oct. 2020, pp. 1152-1164. https://doi.org/10.1038%2Fs41594-020-0512-7.