Cargando…

On the Interaction Between SMARCAL1 and BRG1

SMARCAL1 and BRG1, both classified as ATP-dependent chromatin remodeling proteins, play a role in double-strand break DNA damage response pathways. Mutations in SMARCAL1 cause Schimke Immuno-osseous Dysplasia (SIOD) while mutations in BRG1 are associated with Coffin-Siris Syndrome (CSS4). In HeLa ce...

Descripción completa

Detalles Bibliográficos
Autores principales: Bisht, Deepa, Patne, Ketki, Rakesh, Radhakrishnan, Muthuswami, Rohini
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243424/
https://www.ncbi.nlm.nih.gov/pubmed/35784471
http://dx.doi.org/10.3389/fcell.2022.870815
_version_ 1784738306278293504
author Bisht, Deepa
Patne, Ketki
Rakesh, Radhakrishnan
Muthuswami, Rohini
author_facet Bisht, Deepa
Patne, Ketki
Rakesh, Radhakrishnan
Muthuswami, Rohini
author_sort Bisht, Deepa
collection PubMed
description SMARCAL1 and BRG1, both classified as ATP-dependent chromatin remodeling proteins, play a role in double-strand break DNA damage response pathways. Mutations in SMARCAL1 cause Schimke Immuno-osseous Dysplasia (SIOD) while mutations in BRG1 are associated with Coffin-Siris Syndrome (CSS4). In HeLa cells, SMARCAL1 and BRG1 co-regulate the expression of ATM, ATR, and RNAi genes on doxorubicin-induced DNA damage. Both the proteins are found to be simultaneously present on the promoter of these genes. Based on these results we hypothesized that SMARCAL1 and BRG1 interact with each other forming a complex. In this paper, we validate our hypothesis and show that SMARCAL1 and BRG1 do indeed interact with each other both in the absence and presence of doxorubicin. The formation of these complexes is dependent on the ATPase activity of both SMARCAL1 and BRG1. Using deletion constructs, we show that the HARP domains of SMARCAL1 mediate interaction with BRG1 while multiple domains of BRG1 are probably important for binding to SMARCAL1. We also show that SIOD-associated mutants fail to form a complex with BRG1. Similarly, CSS4-associated mutants of BRG1 fail to interact with SMARCAL1, thus, possibly contributing to the failure of the DNA damage response pathway and pathophysiology associated with SIOD and CSS4.
format Online
Article
Text
id pubmed-9243424
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-92434242022-07-01 On the Interaction Between SMARCAL1 and BRG1 Bisht, Deepa Patne, Ketki Rakesh, Radhakrishnan Muthuswami, Rohini Front Cell Dev Biol Cell and Developmental Biology SMARCAL1 and BRG1, both classified as ATP-dependent chromatin remodeling proteins, play a role in double-strand break DNA damage response pathways. Mutations in SMARCAL1 cause Schimke Immuno-osseous Dysplasia (SIOD) while mutations in BRG1 are associated with Coffin-Siris Syndrome (CSS4). In HeLa cells, SMARCAL1 and BRG1 co-regulate the expression of ATM, ATR, and RNAi genes on doxorubicin-induced DNA damage. Both the proteins are found to be simultaneously present on the promoter of these genes. Based on these results we hypothesized that SMARCAL1 and BRG1 interact with each other forming a complex. In this paper, we validate our hypothesis and show that SMARCAL1 and BRG1 do indeed interact with each other both in the absence and presence of doxorubicin. The formation of these complexes is dependent on the ATPase activity of both SMARCAL1 and BRG1. Using deletion constructs, we show that the HARP domains of SMARCAL1 mediate interaction with BRG1 while multiple domains of BRG1 are probably important for binding to SMARCAL1. We also show that SIOD-associated mutants fail to form a complex with BRG1. Similarly, CSS4-associated mutants of BRG1 fail to interact with SMARCAL1, thus, possibly contributing to the failure of the DNA damage response pathway and pathophysiology associated with SIOD and CSS4. Frontiers Media S.A. 2022-06-16 /pmc/articles/PMC9243424/ /pubmed/35784471 http://dx.doi.org/10.3389/fcell.2022.870815 Text en Copyright © 2022 Bisht, Patne, Rakesh and Muthuswami. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Bisht, Deepa
Patne, Ketki
Rakesh, Radhakrishnan
Muthuswami, Rohini
On the Interaction Between SMARCAL1 and BRG1
title On the Interaction Between SMARCAL1 and BRG1
title_full On the Interaction Between SMARCAL1 and BRG1
title_fullStr On the Interaction Between SMARCAL1 and BRG1
title_full_unstemmed On the Interaction Between SMARCAL1 and BRG1
title_short On the Interaction Between SMARCAL1 and BRG1
title_sort on the interaction between smarcal1 and brg1
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243424/
https://www.ncbi.nlm.nih.gov/pubmed/35784471
http://dx.doi.org/10.3389/fcell.2022.870815
work_keys_str_mv AT bishtdeepa ontheinteractionbetweensmarcal1andbrg1
AT patneketki ontheinteractionbetweensmarcal1andbrg1
AT rakeshradhakrishnan ontheinteractionbetweensmarcal1andbrg1
AT muthuswamirohini ontheinteractionbetweensmarcal1andbrg1