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The PARP3- and ATM-dependent phosphorylation of APLF facilitates DNA double-strand break repair

APLF is a forkhead associated-containing protein with poly(ADP-ribose)-binding zinc finger (PBZ) domains, which undergoes ionizing radiation (IR)-induced and Ataxia-Telangiectasia Mutated (ATM)-dependent phosphorylation at serine-116 (Ser(116)). Here, we demonstrate that the phosphorylation of APLF...

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Autores principales: Fenton, Amanda L., Shirodkar, Purnata, Macrae, Chloe J., Meng, Li, Koch, C. Anne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627606/
https://www.ncbi.nlm.nih.gov/pubmed/23449221
http://dx.doi.org/10.1093/nar/gkt134
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author Fenton, Amanda L.
Shirodkar, Purnata
Macrae, Chloe J.
Meng, Li
Koch, C. Anne
author_facet Fenton, Amanda L.
Shirodkar, Purnata
Macrae, Chloe J.
Meng, Li
Koch, C. Anne
author_sort Fenton, Amanda L.
collection PubMed
description APLF is a forkhead associated-containing protein with poly(ADP-ribose)-binding zinc finger (PBZ) domains, which undergoes ionizing radiation (IR)-induced and Ataxia-Telangiectasia Mutated (ATM)-dependent phosphorylation at serine-116 (Ser(116)). Here, we demonstrate that the phosphorylation of APLF at Ser(116) in human U2OS cells by ATM is dependent on poly(ADP-ribose) polymerase 3 (PARP3) levels and the APLF PBZ domains. The interaction of APLF at sites of DNA damage was diminished by the single substitution of APLF Ser(116) to alanine, and the cellular depletion or chemical inhibition of ATM or PARP3 also altered the level of accumulation of APLF at sites of laser-induced DNA damage and impaired the accumulation of Ser(116)-phosphorylated APLF at IR-induced γH2AX foci in human cells. The data further suggest that ATM and PARP3 participate in a common signalling pathway to facilitate APLF-Ser(116) phosphorylation, which, in turn, appears to be required for efficient DNA double-strand break repair kinetics and cell survival following IR. Collectively, these findings provide a more detailed understanding of the molecular pathway that leads to the phosphorylation of APLF following DNA damage and suggest that Ser(116)-APLF phosphorylation facilitates APLF-dependent double-strand break repair.
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spelling pubmed-36276062013-04-17 The PARP3- and ATM-dependent phosphorylation of APLF facilitates DNA double-strand break repair Fenton, Amanda L. Shirodkar, Purnata Macrae, Chloe J. Meng, Li Koch, C. Anne Nucleic Acids Res Genome Integrity, Repair and Replication APLF is a forkhead associated-containing protein with poly(ADP-ribose)-binding zinc finger (PBZ) domains, which undergoes ionizing radiation (IR)-induced and Ataxia-Telangiectasia Mutated (ATM)-dependent phosphorylation at serine-116 (Ser(116)). Here, we demonstrate that the phosphorylation of APLF at Ser(116) in human U2OS cells by ATM is dependent on poly(ADP-ribose) polymerase 3 (PARP3) levels and the APLF PBZ domains. The interaction of APLF at sites of DNA damage was diminished by the single substitution of APLF Ser(116) to alanine, and the cellular depletion or chemical inhibition of ATM or PARP3 also altered the level of accumulation of APLF at sites of laser-induced DNA damage and impaired the accumulation of Ser(116)-phosphorylated APLF at IR-induced γH2AX foci in human cells. The data further suggest that ATM and PARP3 participate in a common signalling pathway to facilitate APLF-Ser(116) phosphorylation, which, in turn, appears to be required for efficient DNA double-strand break repair kinetics and cell survival following IR. Collectively, these findings provide a more detailed understanding of the molecular pathway that leads to the phosphorylation of APLF following DNA damage and suggest that Ser(116)-APLF phosphorylation facilitates APLF-dependent double-strand break repair. Oxford University Press 2013-04 2013-02-28 /pmc/articles/PMC3627606/ /pubmed/23449221 http://dx.doi.org/10.1093/nar/gkt134 Text en © The Author(s) 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Genome Integrity, Repair and Replication
Fenton, Amanda L.
Shirodkar, Purnata
Macrae, Chloe J.
Meng, Li
Koch, C. Anne
The PARP3- and ATM-dependent phosphorylation of APLF facilitates DNA double-strand break repair
title The PARP3- and ATM-dependent phosphorylation of APLF facilitates DNA double-strand break repair
title_full The PARP3- and ATM-dependent phosphorylation of APLF facilitates DNA double-strand break repair
title_fullStr The PARP3- and ATM-dependent phosphorylation of APLF facilitates DNA double-strand break repair
title_full_unstemmed The PARP3- and ATM-dependent phosphorylation of APLF facilitates DNA double-strand break repair
title_short The PARP3- and ATM-dependent phosphorylation of APLF facilitates DNA double-strand break repair
title_sort parp3- and atm-dependent phosphorylation of aplf facilitates dna double-strand break repair
topic Genome Integrity, Repair and Replication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627606/
https://www.ncbi.nlm.nih.gov/pubmed/23449221
http://dx.doi.org/10.1093/nar/gkt134
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