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Article ; Online: Transcript accumulation rates in the early

Sivaramakrishnan, Priya / Watkins, Cameron / Murray, John Isaac

2023 Volume 9, Issue 34, Page(s) eadi1270

Abstract: Dynamic transcriptional changes are widespread in rapidly dividing developing embryos when cell fate decisions are made quickly. ... ...

Abstract	Dynamic transcriptional changes are widespread in rapidly dividing developing embryos when cell fate decisions are made quickly. The
MeSH term(s)	Animals ; Caenorhabditis elegans/genetics ; Embryo, Mammalian ; Cell Differentiation ; Genomics ; Kinetics ; RNA, Messenger/genetics
Chemical Substances	RNA, Messenger
Language	English
Publishing date	2023-08-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adi1270
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Article ; Online: Silencing the alternative.

Sivaramakrishnan, Priya / Murray, John Isaac

eLife

2019 Volume 8

Abstract: The transcription ... ...

Abstract	The transcription factor
MeSH term(s)	Animals ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins ; Gene Expression Regulation ; Neurons ; Transcription Factors
Chemical Substances	Caenorhabditis elegans Proteins ; Transcription Factors
Language	English
Publishing date	2019-08-06
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.49635
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Article ; Online: Transcription infidelity and genome integrity: the parallax view.

Gordon, Alasdair J E / Sivaramakrishnan, Priya / Halliday, Jennifer A / Herman, Christophe

Transcription

2018 Volume 9, Issue 5, Page(s) 315–320

Abstract: It was recently shown that removal of GreA, a transcription fidelity factor, enhances DNA break repair. This counterintuitive result, arising from unresolved backtracked RNA polymerase impeding DNA resection and thereby facilitating RecA-loading, leads ... ...

Abstract	It was recently shown that removal of GreA, a transcription fidelity factor, enhances DNA break repair. This counterintuitive result, arising from unresolved backtracked RNA polymerase impeding DNA resection and thereby facilitating RecA-loading, leads to an interesting corollary: error-free full-length transcripts and broken chromosomes. Therefore, transcription fidelity may compromise genomic integrity.
MeSH term(s)	DNA/genetics ; DNA/metabolism ; DNA Repair ; DNA Replication ; DNA-Directed RNA Polymerases/genetics ; DNA-Directed RNA Polymerases/metabolism ; Epigenesis, Genetic ; Escherichia coli/genetics ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/metabolism ; Genome, Bacterial ; Single-Cell Analysis ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcription, Genetic ; Transcriptional Elongation Factors/genetics ; Transcriptional Elongation Factors/metabolism
Chemical Substances	Escherichia coli Proteins ; GreA protein, E coli ; GreB protein, E coli ; Transcription Factors ; Transcriptional Elongation Factors ; dksA protein, E coli ; DNA (9007-49-2) ; DNA-Directed RNA Polymerases (EC 2.7.7.6)
Language	English
Publishing date	2018-08-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2646974-1
ISSN	2154-1272 ; 2154-1264
ISSN (online)	2154-1272
ISSN	2154-1264
DOI	10.1080/21541264.2018.1491251
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Article ; Online: How Acts of Infidelity Promote DNA Break Repair: Collision and Collusion Between DNA Repair and Transcription.

Sivaramakrishnan, Priya / Gordon, Alasdair J E / Halliday, Jennifer A / Herman, Christophe

BioEssays : news and reviews in molecular, cellular and developmental biology

2018 Volume 40, Issue 10, Page(s) e1800045

Abstract: Transcription is a fundamental cellular process and the first step in gene regulation. Although RNA polymerase (RNAP) is highly processive, in growing cells the progression of transcription can be hindered by obstacles on the DNA template, such as ... ...

Abstract	Transcription is a fundamental cellular process and the first step in gene regulation. Although RNA polymerase (RNAP) is highly processive, in growing cells the progression of transcription can be hindered by obstacles on the DNA template, such as damaged DNA. The authors recent findings highlight a trade-off between transcription fidelity and DNA break repair. While a lot of work has focused on the interaction between transcription and nucleotide excision repair, less is known about how transcription influences the repair of DNA breaks. The authors suggest that when the cell experiences stress from DNA breaks, the control of RNAP processivity affects the balance between preserving transcription integrity and DNA repair. Here, how the conflict between transcription and DNA double-strand break (DSB) repair threatens the integrity of both RNA and DNA are discussed. In reviewing this field, the authors speculate on cellular paradigms where this equilibrium is well sustained, and instances where the maintenance of transcription fidelity is favored over genome stability.
MeSH term(s)	DNA Breaks, Double-Stranded ; DNA Damage ; DNA Repair/physiology ; DNA-Directed RNA Polymerases/genetics ; DNA-Directed RNA Polymerases/metabolism ; Escherichia coli/genetics ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcription, Genetic
Chemical Substances	Escherichia coli Proteins ; GreA protein, E coli ; Transcription Factors ; dksA protein, E coli ; DNA-Directed RNA Polymerases (EC 2.7.7.6)
Language	English
Publishing date	2018-08-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	50140-2
ISSN	1521-1878 ; 0265-9247
ISSN (online)	1521-1878
ISSN	0265-9247
DOI	10.1002/bies.201800045
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Article: How Acts of Infidelity Promote DNA Break Repair: Collision and Collusion Between DNA Repair and Transcription

Sivaramakrishnan, Priya / Gordon, Alasdair J. E / Halliday, Jennifer A / Herman, Christophe

BioEssays. 2018 Oct., v. 40, no. 10

2018

Abstract	Transcription is a fundamental cellular process and the first step in gene regulation. Although RNA polymerase (RNAP) is highly processive, in growing cells the progression of transcription can be hindered by obstacles on the DNA template, such as damaged DNA. The authors recent findings highlight a trade‐off between transcription fidelity and DNA break repair. While a lot of work has focused on the interaction between transcription and nucleotide excision repair, less is known about how transcription influences the repair of DNA breaks. The authors suggest that when the cell experiences stress from DNA breaks, the control of RNAP processivity affects the balance between preserving transcription integrity and DNA repair. Here, how the conflict between transcription and DNA double‐strand break (DSB) repair threatens the integrity of both RNA and DNA are discussed. In reviewing this field, the authors speculate on cellular paradigms where this equilibrium is well sustained, and instances where the maintenance of transcription fidelity is favored over genome stability.
Keywords	DNA ; DNA damage ; DNA repair ; DNA-directed RNA polymerase ; RNA ; genes ; transcription (genetics)
Language	English
Dates of publication	2018-10
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	REVIEW
ZDB-ID	50140-2
ISSN	1521-1878 ; 0265-9247
ISSN (online)	1521-1878
ISSN	0265-9247
DOI	10.1002/bies.201800045
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Article ; Online: The anterior Hox gene ceh-13 and elt-1/GATA activate the posterior Hox genes nob-1 and php-3 to specify posterior lineages in the C. elegans embryo.

Murray, John Isaac / Preston, Elicia / Crawford, Jeremy P / Rumley, Jonathan D / Amom, Prativa / Anderson, Breana D / Sivaramakrishnan, Priya / Patel, Shaili D / Bennett, Barrington Alexander / Lavon, Teddy D / Hsiao, Erin / Peng, Felicia / Zacharias, Amanda L

PLoS genetics

2022 Volume 18, Issue 5, Page(s) e1010187

Abstract: Hox transcription factors play a conserved role in specifying positional identity during animal development, with posterior Hox genes typically repressing the expression of more anterior Hox genes. Here, we dissect the regulation of the posterior Hox ... ...

Abstract	Hox transcription factors play a conserved role in specifying positional identity during animal development, with posterior Hox genes typically repressing the expression of more anterior Hox genes. Here, we dissect the regulation of the posterior Hox genes nob-1 and php-3 in the nematode C. elegans. We show that nob-1 and php-3 are co-expressed in gastrulation-stage embryos in cells that previously expressed the anterior Hox gene ceh-13. This expression is controlled by several partially redundant transcriptional enhancers. These enhancers act in a ceh-13-dependant manner, providing a striking example of an anterior Hox gene positively regulating a posterior Hox gene. Several other regulators also act positively through nob-1/php-3 enhancers, including elt-1/GATA, ceh-20/ceh-40/Pbx, unc-62/Meis, pop-1/TCF, ceh-36/Otx, and unc-30/Pitx. We identified defects in both cell position and cell division patterns in ceh-13 and nob-1;php-3 mutants, suggesting that these factors regulate lineage identity in addition to positional identity. Together, our results highlight the complexity and flexibility of Hox gene regulation and function and the ability of developmental transcription factors to regulate different targets in different stages of development.
MeSH term(s)	Animals ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Gene Expression Regulation, Developmental ; Genes, Homeobox/genetics ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	CEH-13 protein, C elegans ; Caenorhabditis elegans Proteins ; Homeodomain Proteins ; Transcription Factors
Language	English
Publishing date	2022-05-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1010187
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Article ; Online: Escherichia coli

Neve, Isaiah A A / Sowa, Jessica N / Lin, Chih-Chun J / Sivaramakrishnan, Priya / Herman, Christophe / Ye, Youqiong / Han, Leng / Wang, Meng C

G3 (Bethesda, Md.)

2020 Volume 10, Issue 1, Page(s) 189–198

Abstract: The relationship of genotypes to phenotypes can be modified by environmental inputs. Such crucial environmental inputs include metabolic cues derived from microbes living together with animals. Thus, the analysis of genetic effects on animals' physiology ...

Abstract	The relationship of genotypes to phenotypes can be modified by environmental inputs. Such crucial environmental inputs include metabolic cues derived from microbes living together with animals. Thus, the analysis of genetic effects on animals' physiology can be confounded by variations in the metabolic profile of microbes.
MeSH term(s)	Animals ; Caenorhabditis elegans ; Escherichia coli ; Host-Pathogen Interactions ; Metabolome ; Mitochondria/metabolism ; Phenotype ; RNA Interference
Language	English
Publishing date	2020-01-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2629978-1
ISSN	2160-1836 ; 2160-1836
ISSN (online)	2160-1836
ISSN	2160-1836
DOI	10.1534/g3.119.400741
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Article ; Online: The transcription fidelity factor GreA impedes DNA break repair.

Sivaramakrishnan, Priya / Sepúlveda, Leonardo A / Halliday, Jennifer A / Liu, Jingjing / Núñez, María Angélica Bravo / Golding, Ido / Rosenberg, Susan M / Herman, Christophe

Nature

2017 Volume 550, Issue 7675, Page(s) 214–218

Abstract: Homologous recombination repairs DNA double-strand breaks and must function even on actively transcribed DNA. Because break repair prevents chromosome loss, the completion of repair is expected to outweigh the transcription of broken templates. However, ... ...

Abstract	Homologous recombination repairs DNA double-strand breaks and must function even on actively transcribed DNA. Because break repair prevents chromosome loss, the completion of repair is expected to outweigh the transcription of broken templates. However, the interplay between DNA break repair and transcription processivity is unclear. Here we show that the transcription factor GreA inhibits break repair in Escherichia coli. GreA restarts backtracked RNA polymerase and hence promotes transcription fidelity. We report that removal of GreA results in markedly enhanced break repair via the classic RecBCD-RecA pathway. Using a deep-sequencing method to measure chromosomal exonucleolytic degradation, we demonstrate that the absence of GreA limits RecBCD-mediated resection. Our findings suggest that increased RNA polymerase backtracking promotes break repair by instigating RecA loading by RecBCD, without the influence of canonical Chi signals. The idea that backtracked RNA polymerase can stimulate recombination presents a DNA transaction conundrum: a transcription fidelity factor that compromises genomic integrity.
MeSH term(s)	DNA Breaks, Double-Stranded ; DNA Repair ; DNA-Directed RNA Polymerases/metabolism ; Escherichia coli/enzymology ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Escherichia coli Proteins/metabolism ; Exodeoxyribonuclease V/metabolism ; Protein Binding ; Rec A Recombinases/metabolism ; Transcription Factors/metabolism ; Transcription, Genetic
Chemical Substances	Escherichia coli Proteins ; GreA protein, E coli ; Transcription Factors ; Rec A Recombinases (EC 2.7.7.-) ; DNA-Directed RNA Polymerases (EC 2.7.7.6) ; Exodeoxyribonuclease V (EC 3.1.11.5) ; exodeoxyribonuclease V, E coli (EC 3.1.11.5)
Language	English
Publishing date	2017-10-04
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/nature23907
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Article: Characterization of a Novel RNA Polymerase Mutant That Alters DksA Activity

Satory, Dominik / Halliday, Jennifer A / Sivaramakrishnan, Priya / Lua, Rhonald C / Herman, Christophe

Journal of bacteriology. 2013 Sept. 15, v. 195, no. 18

2013

Abstract: The auxiliary factor DksA is a global transcription regulator and, with the help of ppGpp, controls the nutritional stress response in Escherichia coli. Although the consequences of its modulation of RNA polymerase (RNAP) are becoming better explained, ... ...

Abstract	The auxiliary factor DksA is a global transcription regulator and, with the help of ppGpp, controls the nutritional stress response in Escherichia coli. Although the consequences of its modulation of RNA polymerase (RNAP) are becoming better explained, it is still not fully understood how the two proteins interact. We employed a series of genetic suppressor selections to find residues in RNAP that alter its sensitivity to DksA. Our approach allowed us to identify and genetically characterize in vivo three single amino acid substitutions: β′ E677G, β V146F, and β G534D. We demonstrate that the mutation β′ E677G affects the activity of both DksA and its homolog, TraR, but does not affect the action of other secondary interactors, such as GreA or GreB. Our mutants provide insight into how different auxiliary transcription factors interact with RNAP and contribute to our understanding of how different stages of transcription are regulated through the secondary channel of RNAP in vivo.
Keywords	DNA-directed RNA polymerase ; Escherichia coli ; amino acid substitution ; bacteriology ; malnutrition ; mutants ; proteins ; stress response ; transcription factors
Language	English
Dates of publication	2013-0915
Size	p. 4187-4194.
Publishing place	American Society for Microbiology
Document type	Article
ZDB-ID	2968-3
ISSN	1098-5530 ; 0021-9193
ISSN (online)	1098-5530
ISSN	0021-9193
DOI	10.1128/JB.00382-13
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Article ; Online: H3K9me2 orchestrates inheritance of spatial positioning of peripheral heterochromatin through mitosis.

Poleshko, Andrey / Smith, Cheryl L / Nguyen, Son C / Sivaramakrishnan, Priya / Wong, Karen G / Murray, John Isaac / Lakadamyali, Melike / Joyce, Eric F / Jain, Rajan / Epstein, Jonathan A

eLife

2019 Volume 8

Abstract: Cell-type-specific 3D organization of the genome is unrecognizable during mitosis. It remains unclear how essential positional information is transmitted through cell division such that a daughter cell recapitulates the spatial genome organization of the ...

Abstract	Cell-type-specific 3D organization of the genome is unrecognizable during mitosis. It remains unclear how essential positional information is transmitted through cell division such that a daughter cell recapitulates the spatial genome organization of the parent. Lamina-associated domains (LADs) are regions of repressive heterochromatin positioned at the nuclear periphery that vary by cell type and contribute to cell-specific gene expression and identity. Here we show that histone 3 lysine 9 dimethylation (H3K9me2) is an evolutionarily conserved, specific mark of nuclear peripheral heterochromatin and that it is retained through mitosis. During mitosis, phosphorylation of histone 3 serine 10 temporarily shields the H3K9me2 mark allowing for dissociation of chromatin from the nuclear lamina. Using high-resolution 3D immuno-oligoFISH, we demonstrate that H3K9me2-enriched genomic regions, which are positioned at the nuclear lamina in interphase cells prior to mitosis, re-associate with the forming nuclear lamina before mitotic exit. The H3K9me2 modification of peripheral heterochromatin ensures that positional information is safeguarded through cell division such that individual LADs are re-established at the nuclear periphery in daughter nuclei. Thus, H3K9me2 acts as a 3D architectural mitotic guidepost. Our data establish a mechanism for epigenetic memory and inheritance of spatial organization of the genome.
MeSH term(s)	Animals ; Cell Line ; Heterochromatin/metabolism ; Histones/metabolism ; Humans ; In Situ Hybridization, Fluorescence ; Methylation ; Mitosis ; Phosphorylation ; Protein Processing, Post-Translational ; Wills
Chemical Substances	Heterochromatin ; Histones
Language	English
Publishing date	2019-10-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.49278
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