Cyclin-dependent kinases in DNA damage response

Kciuk, Mateusz; Gielecińska, Adrianna; Mujwar, Somdutt; Mojzych, Mariusz; Kontek, Renata

doi:10.1016/j.bbcan.2022.188716

Cited by 56 publications

(32 citation statements)

References 95 publications

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“…Given the important roles of MYC, PARP1, and TP53 in the DDR pathways, these enzymes have attracted considerable attention. More recently, a more sophisticated role of CDKs in DDR has emerged [ 83 ]. CDK inhibitors have been extensively examined in clinical trials [ 84 , 85 ].…”

Section: Discussionmentioning

confidence: 99%

Cyclin-Dependent Kinase Synthetic Lethality Partners in DNA Damage Response

Kciuk

Gielecińska

Mujwar

et al. 2022

IJMS

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Cyclin-dependent kinases (CDKs) are pivotal mediators and effectors of the DNA damage response (DDR) that regulate both the pathway components and proteins involved in repair processes. Synthetic lethality (SL) describes a situation in which two genes are linked in such a way that the lack of functioning of just one maintains cell viability, while depletion of both triggers cell death. Synthetic lethal interactions involving CDKs are now emerging, and this can be used to selectively target tumor cells with DNA repair defects. In this review, SL interactions of CDKs with protooncogene products MYC, poly (ADP-ribose) polymerase (PARP-1), and cellular tumor antigen p53 (TP53) are discussed. The individual roles of each of the SL partners in DDR are described.

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Section: Discussionmentioning

confidence: 99%

Cyclin-Dependent Kinase Synthetic Lethality Partners in DNA Damage Response

Kciuk

Gielecińska

Mujwar

et al. 2022

IJMS

Self Cite

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“…The most characteristic feature of cancer development is dysregulation of the cell cycle machinery (21). The cell cycle regulatory mechanism is tightly associated with the cellular processes of proliferation, differentiation, and apoptosis (22).…”

Section: Discussionmentioning

confidence: 99%

Cancer related-genes enriched in peripheral blood mononuclear cells (PBMCs) of COVID-19 patients. a bioinformatics study

Ahmadi

Changaei

Teymouri

et al. 2022

Preprint

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BackgroundSince COVID-19 has become one of the biggest challenges for health care systems in the past decade. The SARS-CoV-2 primarily affects the lungs, but many studies implied that other health complications such as brain damage, heart failure, and kidneys dysfunction also are associated with SARS-CoV-2 infection. Many scientific efforts have revealed the clinical and molecular details of SARS-CoV-2 pathogenesis. However, comprehension of COVID-19 complications demands more investigations. In this context, the relation between SARS-CoV-2 infection and cancer has been less addressed. In this regard, we aimed to discover any possible links between SARS-CoV-2 infection and cancer development in a bioinformatics study.MethodsThe pertinent datasets were chosen from the GEO database. COVID-19 was searched for differentially expressed genes where |Log2 FC| > 1 and P < 0.05 were deemed statistically significant. The ClusterProfiler package employed gene ontology and pathway enrichment analysis for common genes. Functional interaction of proteins was predicted using STRING online then Cytoscape analysis was carried out to determine the target genes. Finally, gene set enrichment analysis was performed to find any correlation between candidate genes and different types of cancer.ResultsThe analysis showed that numerous cancer-related genes up-regulated in SARS-CoV-2 infected patients, particularly those genes participating in the cell cycle regulation or engaged in cellular senescence processes.ConclusionOur findings suggest that SARS-CoV-2 can be considered a potential risk factor for increasing the probability of developing cancer.

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“…HR is restricted to the S and G2 phases of the cell cycle due to the cell cycle-dependent availability of sister chromatids. This is also correlated with the fact that cyclin-dependent kinases (CDKs) have a modulatory role on DSB components, including their influence on enzymes involved in HR [ 18 ]. NHEJ is an error-prone process that simply fuses the two broken ends together, whereas HR is error-free, using the genetically identical sister chromatid as a template for repair.…”

Section: Molecular Landscapementioning

confidence: 99%

BRCA Mutations in Ovarian and Prostate Cancer: Bench to Bedside

Boussios

Rassy

Moschetta

et al. 2022

Cancers

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DNA damage repair (DDR) defects are common in different cancer types, and these alterations can be exploited therapeutically. Epithelial ovarian cancer (EOC) is among the tumours with the highest percentage of hereditary cases. BRCA1 and BRCA2 predisposing pathogenic variants (PVs) were the first to be associated with EOC, whereas additional genes comprising the homologous recombination (HR) pathway have been discovered with DNA sequencing technologies. The incidence of DDR alterations among patients with metastatic prostate cancer is much higher compared to those with localized disease. Genetic testing is playing an increasingly important role in the treatment of patients with ovarian and prostate cancer. The development of poly (ADP-ribose) polymerase (PARP) inhibitors offers a therapeutic strategy for patients with EOC. One of the mechanisms of PARP inhibitors exploits the concept of synthetic lethality. Tumours with BRCA1 or BRCA2 mutations are highly sensitive to PARP inhibitors. Moreover, the synthetic lethal interaction may be exploited beyond germline BRCA mutations in the context of HR deficiency, and this is an area of ongoing research. PARP inhibitors are in advanced stages of development as a treatment for metastatic castration-resistant prostate cancer. However, there is a major concern regarding the need to identify reliable biomarkers predictive of treatment response. In this review, we explore the mechanisms of DDR, the potential for genomic analysis of ovarian and prostate cancer, and therapeutics of PARP inhibitors, along with predictive biomarkers.

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Cyclin-dependent kinases in DNA damage response

Cited by 56 publications

References 95 publications

Cyclin-Dependent Kinase Synthetic Lethality Partners in DNA Damage Response

Cyclin-Dependent Kinase Synthetic Lethality Partners in DNA Damage Response

Cancer related-genes enriched in peripheral blood mononuclear cells (PBMCs) of COVID-19 patients. a bioinformatics study

BRCA Mutations in Ovarian and Prostate Cancer: Bench to Bedside

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