2024-03-28T22:32:20Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1805252021-12-27T16:24:18Zcom_10261_134com_10261_1col_10261_387
DIGITAL.CSIC
author
Gavish-Izakson, Michal
author
Velpula, Bhagya Bhavana
author
Elkon, Ran
author
Prados-Carvajal, Rosario
author
Barnabas, Georgina D.
author
Pineiro Ugalde, Alejandro
author
Agami, Reuven
author
Geiger, Tamar
author
Huertas Sánchez, Pablo
author
Ziv, Yael
author
Shiloh, Yosef
funder
Adelson Medical Research Foundation
funder
A-T Children's Project
funder
Israel Science Foundation
funder
National Natural Science Foundation of China
funder
Israel Cancer Research Fund
funder
Ministerio de Economía y Competitividad (España)
funder
European Research Council
funder
Ministerio de Educación, Cultura y Deporte (España)
funder
Netherlands Organization for Scientific Research
funder
Human Frontier Science Program
funder
Ministry of Education (Israel)
2019-04-25T08:55:06Z
2019-04-25T08:55:06Z
2018-01-25
Nucleic Acids Research 46(2): 3351–3365 (2018)
0305-1048
http://hdl.handle.net/10261/180525
10.1093/nar/gkx1240
1362-4962
http://dx.doi.org/10.13039/100001962http://dx.doi.org/10.13039/100004412http://dx.doi.org/10.13039/501100003176http://dx.doi.org/10.13039/100005984http://dx.doi.org/10.13039/501100000781http://dx.doi.org/10.13039/501100001809http://dx.doi.org/10.13039/100001698http://dx.doi.org/10.13039/501100003329http://dx.doi.org/10.13039/501100003977
29253183
The DNA damage response (DDR) is an extensive signaling network that is robustly mobilized by DNA double-strand breaks (DSBs). The primary transducer of the DSB response is the protein kinase, ataxia-telangiectasia, mutated (ATM). Here, we establish nuclear poly(A)-binding protein 1 (PABPN1) as a novel target of ATM and a crucial player in the DSB response. PABPN1 usually functions in regulation of RNA processing and stability. We establish that PABPN1 is recruited to the DDR as a critical regulator of DSB repair. A portion of PABPN1 relocalizes to DSB sites and is phosphorylated on Ser95 in an ATM-dependent manner. PABPN1 depletion sensitizes cells to DSB-inducing agents and prolongs the DSB-induced G2/M cell-cycle arrest, and DSB repair is hampered by PABPN1 depletion or elimination of its phosphorylation site. PABPN1 is required for optimal DSB repair via both nonhomologous end-joining (NHEJ) and homologous recombination repair (HRR), and specifically is essential for efficient DNA-end resection, an initial, key step in HRR. Using mass spectrometry analysis, we capture DNA damage-induced interactions of phospho-PABPN1, including well-established DDR players as well as other RNA metabolizing proteins. Our results uncover a novel ATM-dependent axis in the rapidly growing interface between RNA metabolism and the DDR
eng
openAccess
Nuclear poly(A)-binding protein 1 is an ATM target and essential for DNA double-strand break repair
artículo
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URL
https://digital.csic.es/bitstream/10261/180525/1/Nuclear%20poly_GavishIzakson.pdf
File
MD5
121709af021c2e79ac1946a4f7eb92f6
4944746
application/pdf
Nuclear poly_GavishIzakson.pdf