Constitutive heterochromatin is considered as a functionally inert genome compartment, important for its architecture and stability. How such stable structure is maintained is not well understood. Here, we apply four different visualization schemes to label it and investigate its dynamics during DNA replication and repair. We show that replisomes assemble over the heterochromatin in a temporally ordered manner. Furthermore, heterochromatin undergoes transient decompaction locally at the active sites of DNA synthesis. Using selective laser microirradiation conditions that lead to damage repaired via processive DNA synthesis, we measured similarly local decompaction of heterochromatin. In both cases, we could not observe large-scale movement of heterochromatin to the domain surface. Instead, the processive DNA synthesis machinery assembled at the replication/repair sites. Altogether, our data are compatible with a progression of DNA replication/repair along the chromatin in a dynamic mode with localized and transient decompaction that does not globally remodels the whole heterochromatin compartment.
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http://dx.doi.org/10.1080/19491034.2019.1688932 | DOI Listing |
Cancer Res Commun
January 2025
Zentalis Pharmaceuticals, Inc, San Diego, CA, United States.
KRAS is a potent oncogenic driver which results in downstream hyperactivation of MAPK signaling, while simultaneously increasing replication stress (RS) and accumulation of DNA damage. KRASG12C mutations are common and targetable alterations. Therapeutic inhibition of KRASG12C and eventual resistance to these inhibitors are also known to drive RS and DNA damage through adaptive mechanisms that maintain addiction to high MAPK signaling.
View Article and Find Full Text PDFJ Phys Chem B
January 2025
Intermolecular Interaction Laboratory, Department of Bioinorganic Chemistry, Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, Poland.
This study extends previous research, particularly focusing on patented scientific objects No. ID: PL 240 353 B1, investigating the physicochemical properties of the methyl 3-azido- and 3-amino-2,3-dideoxysaccharides with a nucleoside scaffold similar to 3'-azidothymidine (AZT). The study utilizes multiwavelength spectrophotometric and potentiometric methods to evaluate the ionization of the saccharide units in aqueous solutions.
View Article and Find Full Text PDFRSC Adv
January 2025
Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute, National Research Centre Dokki Giza 12622 Egypt
A novel molecular design based on a quinazolinone scaffold was developed the attachment of aryl alkanesulfonates to the quinazolinone core through a thioacetohydrazide azomethine linker, leading to a new series of quinazolinone-alkanesulfonates 5a-r. The antimicrobial properties of the newly synthesized quinazolinone derivatives 5a-r were investigated to examine their bactericidal and fungicidal activities against bacterial pathogens like , (Gram-positive), , , (Gram-negative), in addition to (unicellular fungal). The tested compounds demonstrated reasonable bactericidal activities compared to standard drugs.
View Article and Find Full Text PDFComput Struct Biotechnol J
December 2024
Systems Biology Center, Key Laboratory of Engineering Biology for Low-carbon Manufacturing, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
DNA holds immense potential as an emerging data storage medium. However, the recovery of information in DNA storage systems faces challenges posed by various errors, including IDS errors, strand breaks, and rearrangements, inevitably introduced during synthesis, amplification, sequencing, and storage processes. Sequence reconstruction, crucial for decoding, involves inferring the DNA reference from a cluster of erroneous copies.
View Article and Find Full Text PDFOncol Lett
March 2025
Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Adiponectin (ADN) regulates DNA synthesis, cell apoptosis and cell cycle to participate in the pathology and progression of glioblastoma. The present study aimed to further explore the effect of ADN on temozolomide (TMZ) resistance in glioblastoma and the underlying mechanism of action. Glioblastoma cell lines (U251 and U87-MG cells) were treated with ADN and TMZ at different concentrations; subsequently, 3.
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