Regulation of DNA damage tolerance in mammalian cells by post-translational modifications of PCNA

Kanao, Rie; Masutani, Chikahide

doi:10.1016/j.mrfmmm.2017.06.004

Cited by 49 publications

(46 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Western blot analysis of PCNA and cell cycle regulators (CDK4, Cyclin D1 and the universal inhibitor of cyclin kinases, p21) in miR-362-5p-inhibitor or GAS7 transfected cells showed a decrease in PCNA, CDK4, and cyclin D1 levels and an increase in p21 levels. PCNA, which is a nuclear protein, is implicated in DNA synthesis and repair [31]. The expression of PCNA is often used to indicate proliferative activity [32].…”

Section: Discussionmentioning

confidence: 99%

miR-362-5p promotes cell proliferation and cell cycle progression by targeting GAS7 in acute myeloid leukemia

Chen

et al. 2020

Human Cell

View full text Add to dashboard Cite

Recently, miR-362-5p has attracted special interest as a novel prognostic predictor in acute myeloid leukemia (AML). However, its biological function and underlying molecular mechanism in AML remain to be further defined. Herein, we found that a significant increase in miR-362-5p expression was observed in AML patients and cell lines using quantitative realtime PCR. The expression of miR-362-5p was altered in THP-1 and HL-60 cells by transfecting with miR-362-5p mimic or inhibitor. A series of experiments showed that inhibition of miR-362-5p expression significantly suppressed cell proliferation, induced G0/G1 phase arrest and attenuated tumor growth in vivo. On the contrary, ectopic expression of miR-362-5p resulted in enhanced cell proliferation, cell cycle progression and tumor growth. Moreover, growth arrest-specific 7 (GAS7) was confirmed as a direct target gene of miR-362-5p and was negatively modulated by miR-362-5p. GAS7 overexpression imitated the tumor suppressive effect of silenced miR-362-5p on THP-1 cells. Furthermore, miR-362-5p knockdown or GAS7 overexpression obviously down-regulated the expression levels of PCNA, CDK4 and cyclin D1, but up-regulated p21 expression. Collectively, our findings demonstrate that miR-362-5p exerts oncogenic effects in AML by directly targeting GAS7, which might provide a promising therapeutic target for AML.

show abstract

Section: Discussionmentioning

confidence: 99%

miR-362-5p promotes cell proliferation and cell cycle progression by targeting GAS7 in acute myeloid leukemia

Chen

et al. 2020

Human Cell

View full text Add to dashboard Cite

show abstract

“…A great deal of oxygen free radicals could result from brain impairment and lead to neuronal base damages which could be repaired by the PCNA-dependent pathway [ 31 ]. Protein expression of PCNA (a DNA repair protein) decreased with PM 2.5 exposure dosage at each time point in mice offspring in the present work.…”

Section: Discussionmentioning

confidence: 99%

Maternal Exposure to PM2.5 during Pregnancy Induces Impaired Development of Cerebral Cortex in Mice Offspring

Zhang

Zheng

Wang

et al. 2018

IJMS

View full text Add to dashboard Cite

Air pollution is a serious environmental health problem closely related to the occurrence of central nervous system diseases. Exposure to particulate matter with an aerodynamic diameter less than or equal to 2.5 µm (PM2.5) during pregnancy may affect the growth and development of infants. The present study was to investigate the effects of maternal exposure to PM2.5 during pregnancy on brain development in mice offspring. Pregnant mice were randomly divided into experimental groups of low-, medium-, or high-dosages of PM2.5, a mock-treated group which was treated with the same amount of phosphate buffer solution (PBS), and acontrol group which was untreated. The ethology of offspring mice on postnatal days 1, 7, 14, 21, and 30, along with neuronal development and apoptosis in the cerebral cortex were investigated. Compared with the control, neuronal mitochondrial cristae fracture, changed autophagy characteristics, significantly increased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cell rate, and mRNA levels of apoptosis-related caspase-8 and caspase-9 were found in cerebral cortex of mice offspring from the treatment groups, with mRNA levels of Bcl-2 and ratio of Bcl-2 to Bax decreased. Treatment groups also demonstrated enhanced protein expressions of apoptosis-related cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9, along with declined proliferating cell nuclear antigen (PCNA), Bcl-2, and ratio of Bcl-2 to Bax. Open field experiments and tail suspension experiments showed that exposure to high dosage of PM2.5 resulted in decreased spontaneous activities but increased static accumulation time in mice offspring, indicating anxiety, depression, and social behavioral changes. Our results suggested that maternal exposure to PM2.5 during pregnancy might interfere with cerebral cortex development in mice offspring by affecting cell apoptosis.

show abstract

“…These DNA damage bypass pathways are largely regulated by the ubiquitylation of PCNA ( Figure 1) [8,[30][31][32][33][34][35][36][37][38][39][40]. The mono-ubiquitylation of PCNA on lysine-164 promotes translesion synthesis [8].…”

Section: Dna Damage Bypass and Pcna Modificationsmentioning

confidence: 99%

Control of DNA Damage Bypass by Ubiquitylation of PCNA

Ripley

Gildenberg

Washington

2020

Genes

View full text Add to dashboard Cite

DNA damage leads to genome instability by interfering with DNA replication. Cells possess several damage bypass pathways that mitigate the effects of DNA damage during replication. These pathways include translesion synthesis and template switching. These pathways are regulated largely through post-translational modifications of proliferating cell nuclear antigen (PCNA), an essential replication accessory factor. Mono-ubiquitylation of PCNA promotes translesion synthesis, and K63-linked poly-ubiquitylation promotes template switching. This article will discuss the mechanisms of how these post-translational modifications of PCNA control these bypass pathways from a structural and biochemical perspective. We will focus on the structure and function of the E3 ubiquitin ligases Rad18 and Rad5 that facilitate the mono-ubiquitylation and poly-ubiquitylation of PCNA, respectively. We conclude by reviewing alternative ideas about how these post-translational modifications of PCNA regulate the assembly of the multi-protein complexes that promote damage bypass pathways.

show abstract

Regulation of DNA damage tolerance in mammalian cells by post-translational modifications of PCNA

Cited by 49 publications

References 99 publications

miR-362-5p promotes cell proliferation and cell cycle progression by targeting GAS7 in acute myeloid leukemia

miR-362-5p promotes cell proliferation and cell cycle progression by targeting GAS7 in acute myeloid leukemia

Maternal Exposure to PM2.5 during Pregnancy Induces Impaired Development of Cerebral Cortex in Mice Offspring

Control of DNA Damage Bypass by Ubiquitylation of PCNA

Contact Info

Product

Resources

About