Publications by authors named "Shereen A Howpay Manage"
Acetylation plays a critical role in regulating eukaryotic transcription via the modification of histones. Beyond this well-documented function, a less explored biological frontier is the potential for acetylation to modify and regulate the function of RNA molecules themselves. -Acetylcytdine (acC) is a minor RNA nucleobase conserved across all three domains of life (archaea, bacteria, and eukarya), a conservation that suggests a fundamental role in biological processes.
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- - The study examines how the DNA repair enzyme APE1 interacts with G-quadruplex (G4) structures in DNA, focusing on the impact of the G4's shape and format due to abasic sites (AP) on this interaction.
- - APE1 was tested with different types of these G4 structures formed from human telomere sequences, revealing that telomere G4 folds were slightly better substrates for APE1 than those found in gene promoters.
- - Findings suggest that the specific topology of G4 structures in gene promoters is important for APE1's binding and regulatory function, although it did not successfully regulate transcription in certain assays.
Article Synopsis
- The study investigates how the DNA repair enzyme APE1 interacts with G-quadruplex (G4) DNA structures that contain an abasic site, which may play a role in gene regulation during oxidative stress.
- Using second harmonic generation (SHG), researchers confirmed that APE1 binds to the G4 folds in a specific and ordered manner, addressing previous uncertainties about this interaction.
- The findings revealed that APE1 has a significant binding affinity (dissociation constant of ~100 nM) for G4 structures compared to standard DNA forms, highlighting SHG as a valuable tool for studying complex DNA-protein interactions in biochemistry.
Article Synopsis
- APE1 is an enzyme involved in base excision repair and gene regulation, particularly during oxidative stress, where it interacts with G-quadruplex (G4) structures and transcription factors.
- The study investigates how cysteine oxidation to sulfenic acid affects APE1's function, revealing that five out of seven cysteine residues are prone to this modification, which can hinder its endonuclease activity while increasing its affinity for G4 binding.
- The findings suggest that cysteine oxidation could shift APE1's role from repairing DNA to modulating gene transcription during oxidative stress, highlighting its importance in cellular responses.
Article Synopsis
- APE1 is an important enzyme that not only repairs DNA damage but also plays a role in regulating gene transcription by interacting with specific DNA structures known as G-quadruplexes (G4s), particularly when there's an abasic site present.
- The study focused on how APE1 binds to and cleaves different DNA types, showing that its activity is influenced by metal ions like potassium (K) and magnesium (Mg) as well as the enzyme's N-terminal domain.
- The research revealed that while APE1 can effectively bind and cleave certain DNA configurations, the presence of a specific ligand (pyridostatin) can inhibit these actions, hinting at potential applications in biological and medicinal fields.
Article Synopsis
- Direct RNA sequencing was used to investigate the epitranscriptomic modification pseudouridine (Ψ) by employing a protein nanopore sensor and a helicase brake to control RNA passage.
- The study discovered that Ψ and uridine (U) can produce different signals in the nanopore sensor depending on their surrounding sequence context, which can lead to biases in sequencing unknown RNA samples.
- To overcome these biases, the researchers found that Ψ's longer dwell time through the helicase brake improved the accuracy of modification detection, leading to the identification of five conserved Ψ sites in the SARS-CoV-2 genome, two of which were validated through additional assays.
Article Synopsis
- The study suggests that a specific G-rich DNA sequence, which can form a G-quadruplex, plays a role in repairing DNA damaged by oxidative stress, particularly the oxidation of guanine to 8-oxo-7,8-dihydroguanine (OG).
- The presence of OG affects gene regulation by altering the DNA structure near where transcription begins, enabling the recruitment of repair proteins, such as OGG1 and APE1, to fix the damage.
- The findings indicate that this G-quadruplex sequence is conserved across many mammals, implying it is evolutionarily important for responding to oxidative stress and may function like an epigenetic switch.