Different SWI/SNF complexes coordinately promote R-loop- and RAD52-dependent transcription-coupled homologous recombination DOI Creative Commons
Carlota Davó-Martínez,

Angela Helfricht,

Cristina Ribeiro-Silva

et al.

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 51(17), P. 9055 - 9074

Published: July 20, 2023

Abstract The SWI/SNF family of ATP-dependent chromatin remodeling complexes is implicated in multiple DNA damage response mechanisms and frequently mutated cancer. BAF, PBAF ncBAF are three major types that functionally distinguished by their exclusive subunits. Accumulating evidence suggests double-strand breaks (DSBs) transcriptionally active preferentially repaired a dedicated homologous recombination pathway. We show different subunits promote rapidly recruited to DSBs transcription-dependent manner. RNA polymerase II eviction near initiate transcriptional silencing, while the BAF complex helps maintain this silencing. Furthermore, ARID1A-containing RNaseH1 RAD52 recruitment facilitate R-loop resolution repair. Our results highlight how perform functions enable repair context actively transcribed genes.

Language: Английский

The Unfolded Protein Response: Detecting and Responding to Fluctuations in the Protein-Folding Capacity of the Endoplasmic Reticulum DOI Open Access
G Elif Karagöz, Diego Acosta‐Alvear, Peter Walter

et al.

Cold Spring Harbor Perspectives in Biology, Journal Year: 2019, Volume and Issue: 11(9), P. a033886 - a033886

Published: Jan. 22, 2019

Most of the secreted and plasma membrane proteins are synthesized on membrane-bound ribosomes endoplasmic reticulum (ER). They require engagement ER-resident chaperones foldases that assist in their folding maturation. Since protein homeostasis ER is crucial for cellular function, protein-folding status organelle's lumen continually surveyed by a network signaling pathways, collectively called unfolded response (UPR). Protein-folding imbalances, or "ER stress," detected highly conserved sensors adjust ER's capacity according to physiological needs cell. We review recent developments field have provided new insights into stress-sensing mechanisms used UPR which they integrate various inputs organelle accommodate fluctuations demands.

Language: Английский

Citations

272
Therapy resistance: opportunities created by adaptive responses to targeted therapies in cancer DOI
Marilyne Labrie, Joan S. Brugge, Gordon B. Mills

et al.

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(6), P. 323 - 339

Published: March 9, 2022

Language: Английский

Citations

234
RNA N6-methyladenosine reader IGF2BP3 regulates cell cycle and angiogenesis in colon cancer DOI Creative Commons
Yang Zhou, Tingfeng Wang, Dejun Wu

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2020, Volume and Issue: 39(1)

Published: Sept. 29, 2020

Abstract Background N6-Methyladenosine (m6A) modification has been implicated in multiple processes for colon cancer development. IGF2BP3 was a newly reported m6A reader, whereas its role remains unclear. Methods The expression of associated enzymes and total level were measured by Western Blotting analysis RNA Methylation Quantification Kit respectively. Cell cycle analyzed flowcytometry. interaction related targets immunoprecipitation (RIP) (MeRIP) assays. Results We investigated all regulated found only the overexpression with progression survival based on Cancer Genome Atlas (TCGA) databases. Additionally, we also demonstrated DNA replication cell cycle. Knockdown significantly repressed percentage S phase as well proliferation. Further research bound to mRNA Cyclin D1 (CCND1, checkpoint G1/S cycle) reduced stability via reading CDS region. Overexpression down-regulated cells completely rescued inhibited similar at VEGF. VEGF reads modification, thus both mRNA. angiogenesis regulating Conclusion CCND1 possible prognosis marker potential therapeutic target cancer.

Language: Английский

Citations

212
Causes and consequences of RNA polymerase II stalling during transcript elongation DOI
Melvin Noé González, Daniel Blears, Jesper Q. Svejstrup

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 22(1), P. 3 - 21

Published: Nov. 18, 2020

Language: Английский

Citations

195
ROS: Basic Concepts, Sources, Cellular Signaling, and its Implications in Aging Pathways DOI Creative Commons
Arthur José Pontes Oliveira de Almeida, Júlio César Pinheiro Lúcio de Oliveira,

Larisse Virgolino da Silva Pontes

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 23

Published: Oct. 19, 2022

Reactive oxygen species (ROS) are bioproducts of cellular metabolism. There is a range molecules with oxidizing properties known as ROS. Despite those being implied negatively in aging and numerous diseases, their key role signaling evident. ROS control several biological processes such inflammation, proliferation, cell death. The redox underlying these events one characteristic the new generation scientists aimed at defining environment. potential, which includes balance sources antioxidant system, implies an important target for understanding cells’ fate derived from signaling. In this review, we summarized chemical, balance, signaling, implications aging.

Language: Английский

Citations

175
PRMT5 function and targeting in cancer DOI Creative Commons
Hyungsoo Kim, Ze’ev A. Ronai

Cell Stress, Journal Year: 2020, Volume and Issue: 4(8), P. 199 - 215

Published: July 24, 2020

Protein methyl transferases play critical roles in numerous regulatory pathways that underlie cancer development, progression and therapy-response. Here we discuss the function of PRMT5, a member nine-member PRMT family, controlling oncogenic processes including tumor intrinsic, as well extrinsic microenvironmental signaling pathways. We PRMT5 effect on histone methylation proteins those involved RNA splicing, cell cycle, death metabolic signaling. In all, highlight importance regulation cancer, which provide foundation for therapeutic modalities targeting PRMT5.

Language: Английский

Citations

170
Aldehyde-driven transcriptional stress triggers an anorexic DNA damage response DOI

Lee Mulderrig,

Juan I. Garaycoechea, Zewen Kelvin Tuong

et al.

Nature, Journal Year: 2021, Volume and Issue: 600(7887), P. 158 - 163

Published: Nov. 24, 2021

Language: Английский

Citations

107
Genome-wide RNA polymerase stalling shapes the transcriptome during aging DOI Creative Commons
Ákos Gyenis, Jiang Chang, Joris J. P. G. Demmers

et al.

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(2), P. 268 - 279

Published: Jan. 19, 2023

Gene expression profiling has identified numerous processes altered in aging, but how these changes arise is largely unknown. Here we combined nascent RNA sequencing and polymerase II chromatin immunoprecipitation followed by to elucidate the underlying mechanisms triggering gene wild-type aged mice. We found that 2-year-old liver, 40% of elongating polymerases are stalled, lowering productive transcription skewing transcriptional output a gene-length-dependent fashion. demonstrate this stress caused endogenous DNA damage explains majority aging most mainly postmitotic organs, specifically affecting hallmark pathways such as nutrient sensing, autophagy, proteostasis, energy metabolism, immune function cellular resilience. Age-related evolutionary conserved from nematodes humans. Thus, accumulation stochastic during deteriorates basal transcription, which establishes age-related transcriptome causes dysfunction key pathways, disclosing functionally underlies major aspects normal aging.

Language: Английский

Citations

91
Epigenetics, DNA damage, and aging DOI Creative Commons

Carolina Soto-Palma,

Laura J. Niedernhofer, Christopher Faulk

et al.

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(16)

Published: Aug. 14, 2022

Over the course of a human lifespan, genome integrity erodes, leading to an increased abundance several types chromatin changes. The DNA lesions (chemical perturbations nucleotides) increases with age, as does number genomic mutations and transcriptional disruptions caused by replication or transcription those lesions, respectively. At epigenetic level, precise methylation patterns degrade, likely causing increasingly stochastic variations in gene expression. Similarly, tight regulation histone modifications begins unravel. instability these mechanisms allows transposon element reactivation remobilization, further mutations, dysregulation, cytoplasmic fragments. This cumulative promotes cell signaling events that drive fate decisions extracellular communications known disrupt tissue homeostasis regeneration. In this Review, we focus on age-related changes their interactions instigate events.

Language: Английский

Citations

90
PARP1-DNA co-condensation drives DNA repair site assembly to prevent disjunction of broken DNA ends DOI Creative Commons
Nagaraja Chappidi, Thomas Quail,

Simon Doll

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(4), P. 945 - 961.e18

Published: Feb. 1, 2024

DNA double-strand breaks (DSBs) are repaired at DSB sites. How sites assemble and how broken is prevented from separating not understood. Here we uncover that the synapsis of mediated by sensor protein poly(ADP-ribose) (PAR) polymerase 1 (PARP1). Using bottom-up biochemistry, reconstitute functional show form through co-condensation PARP1 multimers with DNA. The co-condensates exert mechanical forces to keep ends together become enzymatically active for PAR synthesis. PARylation promotes release recruitment effectors, such as Fused in Sarcoma, which stabilizes against separation, revealing a finely orchestrated order events primes repair. We provide comprehensive model hierarchical assembly condensates explain end effector proteins damage

Language: Английский

Citations

62