Differential Effects of Biomimetic Thymine Dimers and Corresponding Photo-Adducts in Primary Human Keratinocytes and Fibroblasts DOI Creative Commons
Rosanna Monetta,

Domenico Campagna,

Valeria Bartolocci

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(12), P. 1484 - 1484

Published: Nov. 21, 2024

UVB radiation induces DNA damage generating several thymine photo-adducts (TDPs), which can lead to mutations and cellular transformation. The repair pathways preserve genomic stability by recognizing removing photodamage. These side products may affect processes. We previously synthesized novel biomimetic dimers (BTDs) bearing different alkane spacers between nucleobases. Thus, the present study investigates whether BTDs their TDPs modulate safeguard of primary keratinocytes fibroblasts using 2D 3D models. found that p53/p21waf1 pathway is activated in cells similar exposure. Compound 1b also induce a skin model. However, exhibit distinct effects on cell survival. They have protective action keratinocytes, maintain clonogenic ability following treatments. Conversely, compounds pro-apoptotic reduced clonogenicity. Moreover, inflammatory cytokines mainly rather than fibroblasts. Matrix metalloproteinase 1 up-regulated both types after Therefore, act short term as mechanisms helping response. Furthermore, they biological depending photodamage form type.

Language: Английский

Generation of cellular reactive oxygen and nitrogen species by exposure to ultraviolet radiation DOI

Macarena Menoni,

Pablo Alcoba,

Marisol Zuluaga Tamayo

et al.

Biophysical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

Language: Английский

Citations

0
Beyond the Swipe: A Review of Photocatalytic Antimicrobial Biocompatible Touchscreen Technology DOI
Nelson Oshogwue Etafo, Abayomi Bamisaye, Muyideen Olaitan Bamidele

et al.

Applied Materials Today, Journal Year: 2025, Volume and Issue: 44, P. 102697 - 102697

Published: March 30, 2025

Language: Английский

Citations

0
The Intriguing Mystery of RPA Phosphorylation in DNA Double-Strand Break Repair DOI Open Access
Valerie J. Fousek-Schuller, Gloria Borgstahl

Genes, Journal Year: 2024, Volume and Issue: 15(2), P. 167 - 167

Published: Jan. 27, 2024

Human Replication Protein A (RPA) was historically discovered as one of the six components needed to reconstitute simian virus 40 DNA replication from purified components. RPA is now known be involved in all metabolism pathways that involve single-stranded (ssDNA). Heterotrimeric comprises several domains connected by flexible linkers and heavily regulated post-translational modifications (PTMs). The structure has been challenging obtain. Various structural methods have applied, but a complete understanding RPA's structure, its function, how it PTMs yet obtained. This review will summarize recent literature concerning phosphorylated cell cycle, analysis RPA, protein interactions involving regulate activity complex formation double-strand break repair. There are many holes our this research area. We conclude with perspectives for future on control repair cycle.

Language: Английский

Citations

2
Starting DNA Synthesis: Initiation Processes during the Replication of Chromosomal DNA in Humans DOI Open Access
Heinz‐Peter Nasheuer, Anna Marie Meaney

Genes, Journal Year: 2024, Volume and Issue: 15(3), P. 360 - 360

Published: March 14, 2024

The initiation reactions of DNA synthesis are central processes during human chromosomal replication. They separated into two main processes: the events at replication origins, start leading strand for each replicon, and numerous taking place lagging synthesis. In addition, a third mechanism is re-initiation after fork stalling, which takes when lesions hinder progression origins regulated multiple levels, from origin recognition to assembly activation replicative helicase, Cdc45–MCM2-7–GINS (CMG) complex. interactions CMG complex with eukaryotic polymerases, polymerase α-primase, δ ε, forks play pivotal roles in These also important signalling unperturbed stalled forks, “replication stress” events, via ATR (ATM–Rad 3-related protein kinase). essential accurate transfer cells’ genetic information their daughters. Thus, failures dysfunctions these give rise genome instability causing diseases, including cancer. influential review “Hallmarks Cancer: New Dimensions”, Hanahan Weinberg (2022) therefore call fundamental function development process cancer cells. recent years, understanding mechanisms has made substantial progress all will be discussed review.

Language: Английский

Citations

2
PrgE: an OB-fold protein from plasmid pCF10 with striking differences to prototypical bacterial SSBs DOI Creative Commons
Annika Breidenstein, Anaïs Lamy, Cyrielle P. J. Bader

et al.

Life Science Alliance, Journal Year: 2024, Volume and Issue: 7(8), P. e202402693 - e202402693

Published: May 29, 2024

A major pathway for horizontal gene transfer is the transmission of DNA from donor to recipient cells via plasmid-encoded type IV secretion systems (T4SSs). Many conjugative plasmids encode a single-stranded DNA-binding protein (SSB) together with their T4SS. Some these SSBs have been suggested aid in establishing plasmid cell, but many, function remains unclear. Here, we characterize PrgE, proposed SSB Enterococcus faecalis pCF10. We show that PrgE not essential conjugation. Structurally, it has characteristic OB-fold SSBs, very unusual properties. Our DNA-bound structure shows binds ssDNA like beads on string supported by its N-terminal tail. In vitro studies highlight plasticity oligomerization and confirm importance N-terminus. Unlike other both double- equally well. This quaternary assembly properties are different prototypical bacterial SSB, also eukaryotic SSBs.

Language: Английский

Citations

1
HeterozygousRPA2variant as a novel genetic cause of telomere biology disorders DOI Open Access

Rima Kochman,

Ibrahima Ba,

Maïlyn Yates

et al.

Genes & Development, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 4, 2024

Premature telomere shortening or instability is associated with a group of rare and heterogeneous diseases collectively known as biology disorders (TBDs). Here we identified two unrelated individuals clinical manifestations TBDs short telomeres the identical monoallelic variant c.767A>G; Y256C in RPA2 . Although replication protein A2 (RPA2) mutant did not affect ssDNA binding G-quadruplex-unfolding properties RPA, mutation reduced affinity ubiquitin ligase RFWD3 RPA ubiquitination. Using engineered knock-in cell lines, found an accumulation at that trigger ATR activation but caused dysfunctional telomeres. Finally, both patients acquired, subset blood cells, somatic genetic rescue events either POT1 genes TERT promoters to counteract accelerated shortening. Collectively, our study indicates variants represent novel cause TBDs. Our results further support fundamental role complex regulating length stability humans.

Language: Английский

Citations

1
Starting DNA Synthesis: Initiation Processes during the Replication of Chromosomal DNA in Humans DOI Open Access
Heinz‐Peter Nasheuer, Anna Marie Meaney

Published: Feb. 23, 2024

The initiation reactions of DNA synthesis are central processes during human chromosomal replication. They separated into two main processes: the events at replication origins, start leading strand for each replicon, and numerous taking place lagging synthesis. In addition, a third mechanism is re-initiation after fork stalling, which takes when lesions hinder progression origin regulated multiple levels, from recognition to assembly activation replicative helicase, Cdc45-MCM2-7-GINS (CMG) complex. interactions CMG complex with eukaryotic polymerases such as polymerase α-primase (Pol α), δ ε forks play pivotal roles in including signalling unperturbed stalled forks, ‘replication stress’ events, via ATR (ATM-Rad 3-related protein kinase). All these essential accurate transfer cells’ genetic information their daughters. Failures dysfunctions gives rise genome instability followed by diseases cancer. Thus, review ‘Hallmarks Cancer: New Dimensions‘ Hanahan Weinberg (2022) called fundamental function development process cancer cells. recent years, understanding mechanisms has made substantial progress all levels will be discussed review.

Language: Английский

Citations

0
PrgE: an OB-fold protein from plasmid pCF10 with striking differences to prototypical bacterial SSBs DOI Creative Commons
Annika Breidenstein, Anaïs Lamy, Cyrielle P. J. Bader

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 13, 2024

Abstract A major pathway for horizontal gene transfer is the transmission of DNA from donor to recipient cells via plasmid-encoded Type 4 Secretion Systems (T4SS). Many conjugative plasmids encode a single-stranded DNA-binding protein (SSB) together with their T4SS. Some these SSBs have been suggested aid in establishing plasmid cell, but many function remains unclear. Here, we characterize PrgE, proposed SSB Enterococcus faecalis pCF10. We show that PrgE not essential conjugation. Structurally, it has characteristic OB-fold SSBs, very uncharacteristic properties. Our DNA-bound structure shows binds ssDNA like beads on string, and this plasticity PrgEs oligomerization further confirmed by vitro studies. Unlike other both double- equally well. This quaternary assembly properties are different prototypical bacterial SSB, also eukaryotic SSBs.

Language: Английский

Citations

0
Differential Effects of Biomimetic Thymine Dimers and Corresponding Photo-Adducts in Primary Human Keratinocytes and Fibroblasts DOI Creative Commons
Rosanna Monetta,

Domenico Campagna,

Valeria Bartolocci

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(12), P. 1484 - 1484

Published: Nov. 21, 2024

UVB radiation induces DNA damage generating several thymine photo-adducts (TDPs), which can lead to mutations and cellular transformation. The repair pathways preserve genomic stability by recognizing removing photodamage. These side products may affect processes. We previously synthesized novel biomimetic dimers (BTDs) bearing different alkane spacers between nucleobases. Thus, the present study investigates whether BTDs their TDPs modulate safeguard of primary keratinocytes fibroblasts using 2D 3D models. found that p53/p21waf1 pathway is activated in cells similar exposure. Compound 1b also induce a skin model. However, exhibit distinct effects on cell survival. They have protective action keratinocytes, maintain clonogenic ability following treatments. Conversely, compounds pro-apoptotic reduced clonogenicity. Moreover, inflammatory cytokines mainly rather than fibroblasts. Matrix metalloproteinase 1 up-regulated both types after Therefore, act short term as mechanisms helping response. Furthermore, they biological depending photodamage form type.

Language: Английский

Citations

0