Advancements in Ovarian Cancer Research: Targeting DNA Repair Mechanisms and the Role of DNA Polymerase β Inhibitors DOI Open Access
Anutosh Patra, Abhishek Samanta, Anindita Chakraborty

et al.

Biosciences Biotechnology Research Asia, Journal Year: 2024, Volume and Issue: 21(4), P. 1439 - 1449

Published: Dec. 20, 2024

ABSTRACT: Background: Exposure to mutagens causes DNA damage, which, if not repaired properly, can lead diseases like cancer. Ovarian cancer is a major concern for women globally, including in India, as it often diagnosed at an advanced stage, making treatment more challenging. Recent research implicates repair proteins polymerase β (Pol β) development, emphasising the need understand these pathways targeted therapy. This study uses bibliometric analysis explore ovarian and pathways, providing insights future treatment. Materials Methods: Data from 37,539 articles related cancer, β, inhibitors were analysed Dimensions database. Publication distribution, national cooperation, leading authors, trends examined. Results: Variations publication distribution observed across journals, with notable contributions countries Germany, Canada, Netherlands. Prolific authors institutions identified, shedding light on global academic landscape. Co-occurrence revealed thematic clusters, pathophysiology, risk associations, therapeutic targets, genomic research. Conclusion: offers valuable into pathways. It highlights importance of targeting mechanisms therapy suggests opportunities collaboration personalised medicine. Identifying key directions aids advancing our understanding aiming improve patient outcomes.

Language: Английский

MYBL2 maintains stemness and promotes theta-mediated end joining in triple negative breast cancer DOI Creative Commons
Rachel Bayley,

Anna Munsey,

Saira Ahmed

et al.

Published: April 18, 2025

Abstract Triple negative breast cancer (TNBC) has a poor prognosis due to limited treatment options and high metastasis risk. Breast (BC) stem/progenitor cells, also known as tumour initiating are small, difficult target population within the responsible for therapy resistance. MYBL2 overexpression is commonly linked but its role in BC cells remains elusive. To determine of we generated TNBC cell lines with inducible downregulation. Our findings reveal that elevated essential self-renewal, DNA repair, replication stress response these lowering impairs stemness self-renewal both vitro vivo . Accordingly, our functional mechanistic analyses indicate high-MYBL2 exhibit increased sensitivity Polθ inhibitors which lost upon downregulation transcriptional suppression. Combining ATR further enhances this sensitivity, ex vivo. This study thus identifies Polθ/ATR inhibition synthetic lethality strategy eradicate underscores expression biomarker patient stratification treatment.

Language: Английский

Citations

0
The Influence of Circadian Rhythms on DNA Damage Repair in Skin Photoaging DOI Open Access
Zhi Su,

Qianhua Hu,

Xiang Li

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 10926 - 10926

Published: Oct. 11, 2024

Circadian rhythms, the internal timekeeping systems governing physiological processes, significantly influence skin health, particularly in response to ultraviolet radiation (UVR). Disruptions circadian rhythms can exacerbate UVR-induced damage and increase risk of aging cancer. This review explores how affect various aspects physiology pathology, with a special focus on DNA repair. regulation ensures optimal repair following damage, reducing mutation accumulation, enhancing genomic stability. The control over cell proliferation apoptosis further contributes regeneration UVR. Oxidative stress management is another critical area where exert influence. Key genes like brain muscle ARNT-like 1 (BMAL1) locomotor output cycles kaput (CLOCK) modulate activity antioxidant enzymes signaling pathways protect cells from oxidative stress. also inflammatory immune responses by modulating Langerhans other skin. In summary, form complex defense network that manages through precise repair, proliferation, apoptosis, response, stress, hormonal signaling. Understanding these mechanisms provides insights into developing targeted protection improving cancer prevention.

Language: Английский

Citations

1
Assessment of DNA Double Strand Break Repair Activity Using High-throughput and Quantitative Luminescence-based Reporter Assays DOI Open Access
Diego Grande, Eeson Rajendra, Bethany Mason

et al.

Journal of Visualized Experiments, Journal Year: 2024, Volume and Issue: 208

Published: June 14, 2024

The repair of DNA double strand breaks (DSBs) is crucial for the maintenance genome stability and cell viability. DSB (DSBR) in cells mediated through several mechanisms: homologous recombination (HR), non-homologous end joining (NHEJ), microhomology-mediated (MMEJ), single annealing (SSA). Cellular assays are essential to measure proficiency modulation these pathways response various stimuli. Here, we present a suite extrachromosomal reporter that each reconstitution nanoluciferase gene by one four major DSBR cells. Upon transient transfection into interest, pathway-specific substrates can be measured under 24 h detection Nanoluciferase (NanoLuc) luminescence. These robust quantitative, sensitive, titratable, amenable high-throughput screening format. properties provide broad applications research drug discovery, complementing currently available toolkit cellular assays.

Language: Английский

Citations

0
JoVE Video Dataset DOI Open Access
Diego Grande, Eeson Rajendra, Bethany Mason

et al.

Published: June 15, 2024

The repair of DNA double strand breaks (DSBs) is crucial for the maintenance genome stability and cell viability. DSB (DSBR) in cells mediated through several mechanisms: homologous recombination (HR), non-homologous end joining (NHEJ), microhomology-mediated (MMEJ), single annealing (SSA). Cellular assays are essential to measure proficiency modulation these pathways response various stimuli. Here, we present a suite extrachromosomal reporter that each reconstitution nanoluciferase gene by one four major DSBR cells. Upon transient transfection into interest, pathway-specific substrates can be measured under 24 h detection Nanoluciferase (NanoLuc) luminescence. These robust quantitative, sensitive, titratable, amenable high-throughput screening format. properties provide broad applications research drug discovery, complementing currently available toolkit cellular assays.

Language: Английский

Citations

0
Advancements in Ovarian Cancer Research: Targeting DNA Repair Mechanisms and the Role of DNA Polymerase β Inhibitors DOI Open Access
Anutosh Patra, Abhishek Samanta, Anindita Chakraborty

et al.

Biosciences Biotechnology Research Asia, Journal Year: 2024, Volume and Issue: 21(4), P. 1439 - 1449

Published: Dec. 20, 2024

ABSTRACT: Background: Exposure to mutagens causes DNA damage, which, if not repaired properly, can lead diseases like cancer. Ovarian cancer is a major concern for women globally, including in India, as it often diagnosed at an advanced stage, making treatment more challenging. Recent research implicates repair proteins polymerase β (Pol β) development, emphasising the need understand these pathways targeted therapy. This study uses bibliometric analysis explore ovarian and pathways, providing insights future treatment. Materials Methods: Data from 37,539 articles related cancer, β, inhibitors were analysed Dimensions database. Publication distribution, national cooperation, leading authors, trends examined. Results: Variations publication distribution observed across journals, with notable contributions countries Germany, Canada, Netherlands. Prolific authors institutions identified, shedding light on global academic landscape. Co-occurrence revealed thematic clusters, pathophysiology, risk associations, therapeutic targets, genomic research. Conclusion: offers valuable into pathways. It highlights importance of targeting mechanisms therapy suggests opportunities collaboration personalised medicine. Identifying key directions aids advancing our understanding aiming improve patient outcomes.

Language: Английский

Citations

0