Transcriptional Regulation of Atp-Dependent Chromatin Remodeling Factors: Smarcal1 and Brg1 Mutually Co-Regulate Each Other

Haokip, Dominic Thangminlen; Goel, Isha; Arya, Vijendra; Sharma, Tapan; Kumari, Reshma; Priya, R. S.; Singh, Manpreet; Muthuswami, Rohini

doi:10.1038/srep20532

Cited by 21 publications

(47 citation statements)

References 42 publications

(65 reference statements)

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“…One report suggests SMARCAL1 localization is cell cycle regulated where it is predominately nuclear during S phase through mitosis but is exported to the cytoplasm during the first growth phase of the cell cycle (G 1 ) (Haokip et al , 2016). This study also indicated SMARCAL1 transcript expression is DNA damage-dependent (Haokip et al , 2016). However, these observations require further validation in additional systems.…”

Section: Smarcal1mentioning

confidence: 99%

“…SMARCAL1 also has been reported to have a regulatory role in the transcription of a subset of genes (Baradaran-Heravi et al , 2012b, Sharma et al , 2015, Haokip et al , 2016, Patne et al , 2017). Specifically, SMARCAL1 was reported to directly modify the chromatin near promoter sequences to regulate gene expression especially in cells experiencing replication stress (Sharma et al , 2015, Haokip et al , 2016, Patne et al , 2017).…”

Section: Smarcal1mentioning

confidence: 99%

“…Specifically, SMARCAL1 was reported to directly modify the chromatin near promoter sequences to regulate gene expression especially in cells experiencing replication stress (Sharma et al , 2015, Haokip et al , 2016, Patne et al , 2017). However, SMARCAL1 binds DNA in a sequence independent manner and has not been found in complexes with any transcription factors or components of ATP-dependent chromatin remodeling complexes (Betous et al , 2012).…”

Section: Smarcal1mentioning

confidence: 99%

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Functions of SMARCAL1, ZRANB3, and HLTF in maintaining genome stability

Poole

Chen

2017

Critical Reviews in Biochemistry and Molecular Biology

115

105

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A large number of SNF2 family, DNA and ATP-dependent motor proteins are needed during transcription, DNA replication, and DNA repair to manipulate protein-DNA interactions and change DNA structure. SMARCAL1, ZRANB3, and HLTF are three related members of this family with specialized functions that maintain genome stability during DNA replication. These proteins are recruited to replication forks through protein-protein interactions and bind DNA using both their motor and substrate recognition domains (SRD). The SRD provides specificity to DNA structures like forks and junctions and confer DNA remodeling activity to the motor domains. Remodeling reactions include fork reversal and branch migration to promote fork stabilization, template switching, and repair. Regulation ensures these powerful activities remain controlled and restricted to damaged replication forks. Inherited mutations in SMARCAL1 cause a severe developmental disorder and mutations in ZRANB3 and HLTF are linked to cancer illustrating the importance of these enzymes in ensuring complete and accurate DNA replication. In this review, we examine how these proteins function, concentrating on their common and unique attributes and regulatory mechanisms.

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Section: Smarcal1mentioning

confidence: 99%

Section: Smarcal1mentioning

confidence: 99%

Section: Smarcal1mentioning

confidence: 99%

See 1 more Smart Citation

Functions of SMARCAL1, ZRANB3, and HLTF in maintaining genome stability

Poole

Chen

2017

Critical Reviews in Biochemistry and Molecular Biology

115

105

View full text Add to dashboard Cite

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“…2B; Supplementary Excel File 3 and 4). Previously, we had shown that SMARCAL1 was present on BRG1 promoter and BRG1 was present on SMARCAL1 promoter 24 . The ChIP-seq data validated our experimental results ( Fig.…”

Section: The Transcriptomic Profile Of Hela Cells Is Altered On Treatmentioning

confidence: 95%

“…1G). The ATPase activity of these proteins is needed for co-regulating transcription [24][25][26][27] . Also, we had previously shown that cell line resistant to ADAADiN showed decreased ATPase activity of SMARCAL1 and BRG1 that manifested in alterations in the transcriptomic profile of the cells 6 .…”

Section: The Transcriptomic Profile Of Hela Cells Is Altered On Treatmentioning

confidence: 99%

Altering Mammalian Transcription Networking with Adaadi: An Inhibitor of Atp-Dependent Chromatin Remodeling

Radhakrishnan

Hussain

Goel

et al. 2019

Preprint

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Running title: Altering mammalian transcriptome with ADAADi ABSTRACT Transcriptional control has been earnestly pursued for the regulation of cellular proliferation associated with cancer progression. The foundational paradigm of targeting transcription factors has yielded exquisite specificity, but many factors cannot yet be targeted. In contrast, targeting epigenetic factors to control chromatin structure and consequential gene expression generally yields more global effects on transcription. Our working paradigm targets neither specific transcription factors nor global epigenetic factors but ATP-dependent chromatin remodeling factors that regulate expression of a limited set of genes. Active DNA-dependent ATPase A Domain inhibitor (ADAADi) synthesized by aminoglycoside phosphotransferases is the first-inclass inhibitor of ATP-dependent chromatin remodeling proteins that targets the ATPase domain of these proteins. Mammalian cells are sensitive to ADAADi but cell lines are variable in their individual responses to the inhibitor. The ADAADi product can be generated from a variety of aminoglycoside substrates with cells showing differential responses to ADAADi depending on the starting aminoglycoside. RNA seq analysis demonstrated that targeting the chromatin remodeling by treatment with a sub-lethal concentration of ADAADi yields alterations to the transcriptional network of the cell. Predominantly, the tumor-promoting genes were repressed while pro-apoptotic and tumor suppressors genes were upregulated on treatment with ADAADi, leading to apoptotic-type cell death. Treatment with ADAADi reversed the EMT process as well as inhibited migration of cells and their colony forming ability. In conjunction with the previous report that treatment with ADAADi regresses tumors in mouse model, this chromatin remodeling inhibitor shows promising anti-tumor properties by targeting the main hallmarks of cancer.

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SMARCAL1, the annealing helicase and the transcriptional co‐regulator

et al. 2020

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The ATP‐dependent chromatin remodeling proteins play an important role in DNA repair. The energy released by ATP hydrolysis is used for myriad functions ranging from nucleosome repositioning and nucleosome eviction to histone variant exchange. In addition, the distant member of the family, SMARCAL1, uses the energy to reanneal stalled replication forks in response to DNA damage. Biophysical studies have shown that this protein has the unique ability to recognize and bind specifically to DNA structures possessing double‐strand to single‐strand transition regions. Mutations in SMARCAL1 have been linked to Schimke immuno‐osseous dysplasia, an autosomal recessive disorder that exhibits variable penetrance and expressivity. It has long been hypothesized that the variable expressivity and pleiotropic phenotypes observed in the patients might be due to the ability of SMARCAL1 to co‐regulate the expression of a subset of genes within the genome. Recently, the role of SMARCAL1 in regulating transcription has been delineated. In this review, we discuss the biophysical and functional properties of the protein that help it to transcriptionally co‐regulate DNA damage response as well as to bind to the stalled replication fork and stabilize it, thus ensuring genomic stability. We also discuss the role of SMARCAL1 in cancer and the possibility of using this protein as a chemotherapeutic target.

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Transcriptional Regulation of Atp-Dependent Chromatin Remodeling Factors: Smarcal1 and Brg1 Mutually Co-Regulate Each Other

Cited by 21 publications

References 42 publications

Functions of SMARCAL1, ZRANB3, and HLTF in maintaining genome stability

Functions of SMARCAL1, ZRANB3, and HLTF in maintaining genome stability

Altering Mammalian Transcription Networking with Adaadi: An Inhibitor of Atp-Dependent Chromatin Remodeling

SMARCAL1, the annealing helicase and the transcriptional co‐regulator

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