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SMARCAD1 Phosphorylation and Ubiquitination Are Required for Resection during DNA Double-Strand Break Repair

The chromatin remodeling factor SMARCAD1, an SWI/SNF ATPase family member, has a role in 5′ end resection at DNA double-strand breaks (DSBs) to produce single-strand DNA (ssDNA), a critical step for subsequent checkpoint and repair factor loading to remove DNA damage. However, the mechanistic detail...

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Autores principales: Chakraborty, Sharmistha, Pandita, Raj K., Hambarde, Shashank, Mattoo, Abid R., Charaka, Vijaya, Ahmed, Kazi M., Iyer, Swaminathan P., Hunt, Clayton R., Pandita, Tej K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993204/
https://www.ncbi.nlm.nih.gov/pubmed/29888761
http://dx.doi.org/10.1016/j.isci.2018.03.016
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author Chakraborty, Sharmistha
Pandita, Raj K.
Hambarde, Shashank
Mattoo, Abid R.
Charaka, Vijaya
Ahmed, Kazi M.
Iyer, Swaminathan P.
Hunt, Clayton R.
Pandita, Tej K.
author_facet Chakraborty, Sharmistha
Pandita, Raj K.
Hambarde, Shashank
Mattoo, Abid R.
Charaka, Vijaya
Ahmed, Kazi M.
Iyer, Swaminathan P.
Hunt, Clayton R.
Pandita, Tej K.
author_sort Chakraborty, Sharmistha
collection PubMed
description The chromatin remodeling factor SMARCAD1, an SWI/SNF ATPase family member, has a role in 5′ end resection at DNA double-strand breaks (DSBs) to produce single-strand DNA (ssDNA), a critical step for subsequent checkpoint and repair factor loading to remove DNA damage. However, the mechanistic details of SMARCAD1 coupling to the DNA damage response and repair pathways remains unknown. Here we report that SMARCAD1 is recruited to DNA DSBs through an ATM-dependent process. Depletion of SMARCAD1 reduces ionizing radiation (IR)-induced repairosome foci formation and DSB repair by homologous recombination (HR). IR induces SMARCAD1 phosphorylation at a conserved T906 by ATM kinase, a modification essential for SMARCAD1 recruitment to DSBs. Interestingly, T906 phosphorylation is also important for SMARCAD1 ubiquitination by RING1 at K905. Both these post-translational modifications are critical for regulating the role of SMARCAD1 in DNA end resection, HR-mediated repair, and cell survival after DNA damage.
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spelling pubmed-59932042018-06-08 SMARCAD1 Phosphorylation and Ubiquitination Are Required for Resection during DNA Double-Strand Break Repair Chakraborty, Sharmistha Pandita, Raj K. Hambarde, Shashank Mattoo, Abid R. Charaka, Vijaya Ahmed, Kazi M. Iyer, Swaminathan P. Hunt, Clayton R. Pandita, Tej K. iScience Article The chromatin remodeling factor SMARCAD1, an SWI/SNF ATPase family member, has a role in 5′ end resection at DNA double-strand breaks (DSBs) to produce single-strand DNA (ssDNA), a critical step for subsequent checkpoint and repair factor loading to remove DNA damage. However, the mechanistic details of SMARCAD1 coupling to the DNA damage response and repair pathways remains unknown. Here we report that SMARCAD1 is recruited to DNA DSBs through an ATM-dependent process. Depletion of SMARCAD1 reduces ionizing radiation (IR)-induced repairosome foci formation and DSB repair by homologous recombination (HR). IR induces SMARCAD1 phosphorylation at a conserved T906 by ATM kinase, a modification essential for SMARCAD1 recruitment to DSBs. Interestingly, T906 phosphorylation is also important for SMARCAD1 ubiquitination by RING1 at K905. Both these post-translational modifications are critical for regulating the role of SMARCAD1 in DNA end resection, HR-mediated repair, and cell survival after DNA damage. Elsevier 2018-03-27 /pmc/articles/PMC5993204/ /pubmed/29888761 http://dx.doi.org/10.1016/j.isci.2018.03.016 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Chakraborty, Sharmistha
Pandita, Raj K.
Hambarde, Shashank
Mattoo, Abid R.
Charaka, Vijaya
Ahmed, Kazi M.
Iyer, Swaminathan P.
Hunt, Clayton R.
Pandita, Tej K.
SMARCAD1 Phosphorylation and Ubiquitination Are Required for Resection during DNA Double-Strand Break Repair
title SMARCAD1 Phosphorylation and Ubiquitination Are Required for Resection during DNA Double-Strand Break Repair
title_full SMARCAD1 Phosphorylation and Ubiquitination Are Required for Resection during DNA Double-Strand Break Repair
title_fullStr SMARCAD1 Phosphorylation and Ubiquitination Are Required for Resection during DNA Double-Strand Break Repair
title_full_unstemmed SMARCAD1 Phosphorylation and Ubiquitination Are Required for Resection during DNA Double-Strand Break Repair
title_short SMARCAD1 Phosphorylation and Ubiquitination Are Required for Resection during DNA Double-Strand Break Repair
title_sort smarcad1 phosphorylation and ubiquitination are required for resection during dna double-strand break repair
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993204/
https://www.ncbi.nlm.nih.gov/pubmed/29888761
http://dx.doi.org/10.1016/j.isci.2018.03.016
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