scholarly journals RecQL4 regulates autophagy and apoptosis in U2OS cells

2016 ◽  
Vol 94 (6) ◽  
pp. 551-559 ◽  
Author(s):  
Yangmiao Duan ◽  
Hongbo Fang
Keyword(s):  
Genomic Stability ◽  
Premature Aging ◽  
Mitochondrial Content ◽  
Mitochondrial Stress ◽  
Recq Helicases ◽  
Rnai Technology ◽  
U2os Cells

RecQL4, one of the 5 human RecQ helicases, is a key mediator of genomic stability and its deficiency can cause premature aging phenotypes. Here, by using CRISPR/Cas and RNAi technology, we demonstrated that autophagy level was elevated in both RecQL4 knockdown and knockout cells compared with those of the control cells. Surprisingly, mitochondrial content was increased and LC3 co-localization with mitochondria was partially lost in RecQL4 knockout cells compared with the control cells, suggesting that RecQL4 deficiency impaired mitophagic processes in U2OS cells. Furthermore, we found that knockout of RecQL4 destabilized PINK1. In addition, RecQL4 knockout cells were more susceptible to apoptosis under mitochondrial stress than the control cells. In conclusion, our findings indicated a novel role of RecQL4 in the regulation of autophagy/mitophagy in U2OS cells.

scholarly journals Mechanisms of RecQ helicases in pathways of DNA metabolism and maintenance of genomic stability

2006 ◽  
Vol 398 (3) ◽  
pp. 319-337 ◽  
Author(s):  
Sudha Sharma ◽  
Kevin M. Doherty ◽  
Robert M. Brosh
Keyword(s):  
Protein Interactions ◽  
Human Disease ◽  
Genome Stability ◽  
Molecular Motor ◽  
Genomic Stability ◽  
Premature Aging ◽  
Dna Metabolism ◽  
Dna Helicases ◽  
Recq Helicases ◽  
Hydrolysis Of

Helicases are molecular motor proteins that couple the hydrolysis of NTP to nucleic acid unwinding. The growing number of DNA helicases implicated in human disease suggests that their vital specialized roles in cellular pathways are important for the maintenance of genome stability. In particular, mutations in genes of the RecQ family of DNA helicases result in chromosomal instability diseases of premature aging and/or cancer predisposition. We will discuss the mechanisms of RecQ helicases in pathways of DNA metabolism. A review of RecQ helicases from bacteria to human reveals their importance in genomic stability by their participation with other proteins to resolve DNA replication and recombination intermediates. In the light of their known catalytic activities and protein interactions, proposed models for RecQ function will be summarized with an emphasis on how this distinct class of enzymes functions in chromosomal stability maintenance and prevention of human disease and cancer.

The role of telomeres and vitamin D in cellular aging and age-related diseases

2015 ◽  
Vol 53 (11) ◽  
Author(s):  
Irene Pusceddu ◽  
Christopher-John L. Farrell ◽  
Angela Maria Di Pierro ◽  
Erika Jani ◽  
Wolfgang Herrmann ◽  
...  
Keyword(s):  
Vitamin D ◽  
Genomic Stability ◽  
Cellular Aging ◽  
Premature Aging ◽  
Age Related ◽  
Complex Biological Process ◽  
Increased Risk ◽  
Telomere Biology

AbstractAging is a complex biological process characterized by a progressive decline of organ functions leading to an increased risk of age-associated diseases and death. Decades of intensive research have identified a range of molecular and biochemical pathways contributing to aging. However, many aspects regarding the regulation and interplay of these pathways are insufficiently understood. Telomere dysfunction and genomic instability appear to be of critical importance for aging at a cellular level. For example, age-related diseases and premature aging syndromes are frequently associated with telomere shortening. Telomeres are repetitive nucleotide sequences that together with the associated sheltrin complex protect the ends of chromosomes and maintain genomic stability. Recent studies suggest that micronutrients, such as vitamin D, folate and vitamin B12, are involved in telomere biology and cellular aging. In particular, vitamin D is important for a range of vital cellular processes including cellular differentiation, proliferation and apoptosis. As a result of the multiple functions of vitamin D it has been speculated that vitamin D might play a role in telomere biology and genomic stability. Here we review existing knowledge about the link between telomere biology and cellular aging with a focus on the role of vitamin D. We searched the literature up to November 2014 for human studies, animal models and in vitro experiments that addressed this topic.

scholarly journals The epigenetic regulator LSH maintains fork protection and genomic stability via MacroH2A deposition and RAD51 filament formation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiaoping Xu ◽  
Kai Ni ◽  
Yafeng He ◽  
Jianke Ren ◽  
Chongkui Sun ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Critical Role ◽  
Genomic Stability ◽  
Dna Degradation ◽  
Replication Forks ◽  
Filament Formation ◽  
Epigenetic Regulator ◽  
Centromeric Instability ◽  
Stalled Replication Forks

AbstractThe Immunodeficiency Centromeric Instability Facial Anomalies (ICF) 4 syndrome is caused by mutations in LSH/HELLS, a chromatin remodeler promoting incorporation of histone variant macroH2A. Here, we demonstrate that LSH depletion results in degradation of nascent DNA at stalled replication forks and the generation of genomic instability. The protection of stalled forks is mediated by macroH2A, whose knockdown mimics LSH depletion and whose overexpression rescues nascent DNA degradation. LSH or macroH2A deficiency leads to an impairment of RAD51 loading, a factor that prevents MRE11 and EXO1 mediated nascent DNA degradation. The defect in RAD51 loading is linked to a disbalance of BRCA1 and 53BP1 accumulation at stalled forks. This is associated with perturbed histone modifications, including abnormal H4K20 methylation that is critical for BRCA1 enrichment and 53BP1 exclusion. Altogether, our results illuminate the mechanism underlying a human syndrome and reveal a critical role of LSH mediated chromatin remodeling in genomic stability.

The Role of Cellular Senescence in Werner Syndrome: Toward Therapeutic Intervention in Human Premature Aging

2007 ◽  
Vol 1100 (1) ◽  
pp. 455-469 ◽  
Author(s):  
T. DAVIS ◽  
F. S. WYLLIE ◽  
M. J. ROKICKI ◽  
M. C. BAGLEY ◽  
D. KIPLING
Keyword(s):  
Cellular Senescence ◽  
Therapeutic Intervention ◽  
Werner Syndrome ◽  
Premature Aging

scholarly journals Syntaxin-17-Dependent Mitochondrial Dynamics is Essential for Protection Against Oxidative-Stress-Induced Apoptosis

Antioxidants ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 522 ◽  
Author(s):  
Wang ◽  
Xiao ◽  
Huang ◽  
Liu
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Autophagic Flux ◽  
Wild Type ◽  
Dual Roles ◽  
Defective Mutant ◽  
U2os Cells ◽  
Induced Apoptosis

In this study, cell death induced by the oxidant tert-butylhydroperoxide (tBH) was observed in U2OS cells; this phenotype was rescued by Syntaxin 17 (STX17) knockout (KO) but the mechanism is unknown. STX17 plays dual roles in autophagosome–lysosome fusion and mitochondrial fission. However, the contribution of the two functions of STX17 to apoptosis has not been extensively studied. Here, we sought to dissect the dual roles of STX17 in oxidative-stress-induced apoptosis by taking advantage of STX17 knockout cells and an autophagosome–lysosome fusion defective mutant of STX17. We generated STX17 knockout U2OS cells using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and the STX17 knockout cells were reconstituted with wild-type STX17 and its autophagosome–lysosome fusion defective mutant. Autophagy was assessed by autophagic flux assay, Monomer red fluorescent protein (mRFP)–GFP–LC3 assay and protease protection assay. Golgi, endoplasmic reticulum (ER)/ER–Golgi intermediate compartment (ERGIC) and mitochondrial dynamics were examined by staining the different indicator proteins. Apoptosis was evaluated by caspase cleavage assay. The general reactive oxygen species (ROS) were detected by flow cytometry. In STX17 complete knockout cells, sealed autophagosomes were efficiently formed but their fusion with lysosomes was less defective. The fusion defect was rescued by wild-type STX17 but not the autophagosome–lysosome fusion defective mutant. No obvious defects in Golgi, ERGIC or ER dynamics were observed. Mitochondria were significantly elongated, supporting a role of STX17 in mitochondria fission and the elongation caused by STX17 KO was reversed by the autophagosome–lysosome fusion defective mutant. The clearance of protein aggregation was compromised, correlating with the autophagy defect but not with mitochondrial dynamics. This study revealed a mixed role of STX17 in autophagy, mitochondrial dynamics and oxidative stress response. STX17 knockout cells were highly resistant to oxidative stress, largely due to the function of STX17 in mitochondrial fission rather than autophagy.

scholarly journals ANLN promotes carcinogenesis in oral cancer by regulating the PI3K/mTOR signaling pathway

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Bing Wang ◽  
Xiao-li Zhang ◽  
Chen-xi Li ◽  
Ning-ning Liu ◽  
Min Hu ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Signaling Pathway ◽  
Cell Cycle Progression ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Cell Behaviors ◽  
Rnai Technology ◽  
Tumor Tissues ◽  
Pi3k Signaling Pathway

Abstract Background Oral cancer is a malignant disease that threatenshuman life and greatly reducespatientquality of life. ANLN was reported to promote the progression of cancer. This study aims to investigate the role of ANLNin oral cancer and the underlying molecular mechanism. Methods ANLN expression was downregulated by RNAi technology. The effect of ANLN on cell behaviors, including proliferation, cell cycle progression, invasion, and apoptosis, was detected. Western blotting analysis was used to explore the mechanism by whichANLN functions in oral cancer. Results Data from TCGA database showed that ANLN was expressed at significantly higher levels in tumor tissues thanin normal control tissues. Patients with higher ANLN expression exhibitedshorter survivaltimes. ANLN was alsoabundantly expressedin the cancer cell lines CAL27 and HN30. When ANLN was knocked down in CAL27 and HN30 cells, cell proliferation and colony formation weredecreased. The cell invasion ability was also inhibited. However, the cell apoptosis rate was increased. In addition, the levels of critical members of the PI3K signaling pathway, includingPI3K, mTOR, Akt, and PDK-1, were significantlyreducedafter ANLN was knocked down in CAL27 cells. Conclusions ANLN contributes to oral cancerprogressionand affects activation ofthe PI3K/mTOR signaling pathway. This study providesa new potential targetfor drug development and treatment in oral cancer.

scholarly journals RecQ helicases: suppressors of tumorigenesis and premature aging

2003 ◽  
Vol 374 (3) ◽  
pp. 577-606 ◽  
Author(s):  
Csanád Z. BACHRATI ◽  
Ian D. HICKSON
Keyword(s):  
Replication Fork ◽  
Germ Line ◽  
Genetic Disorders ◽  
Premature Aging ◽  
Recq Helicase ◽  
Dna Helicases ◽  
Recq Helicases ◽  
Protein Partners ◽  
Line Defects ◽  
Rothmund Thomson Syndrome

The RecQ helicases represent a subfamily of DNA helicases that are highly conserved in evolution. Loss of RecQ helicase function leads to a breakdown in the maintenance of genome integrity, in particular hyper-recombination. Germ-line defects in three of the five known human RecQ helicases give rise to defined genetic disorders associated with cancer predisposition and/or premature aging. These are Bloom's syndrome, Werner's syndrome and Rothmund–Thomson syndrome, which are caused by defects in the genes BLM, WRN and RECQ4 respectively. Here we review the properties of RecQ helicases in organisms from bacteria to humans, with an emphasis on the biochemical functions of these enzymes and the range of protein partners that they operate with. We will discuss models in which RecQ helicases are required to protect against replication fork demise, either through prevention of fork breakdown or restoration of productive DNA synthesis.

scholarly journals The role of RecQ helicases in non-homologous end-joining

2014 ◽  
Vol 49 (6) ◽  
pp. 463-472 ◽  
Author(s):  
Guido Keijzers ◽  
Scott Maynard ◽  
Raghavendra A. Shamanna ◽  
Lene Juel Rasmussen ◽  
Deborah L. Croteau ◽  
...  
Keyword(s):  
End Joining ◽  
Recq Helicases ◽  
Non Homologous End Joining

The role of p53 in regulating genomic stability when DNA and RNA synthesis are inhibited

1995 ◽  
Vol 20 (10) ◽  
pp. 431-434 ◽  
Author(s):  
Olga B. Chernova ◽  
Michail V. Chernov ◽  
Munna L. Agarwal ◽  
William R. Taylor ◽  
George R. Stark
Keyword(s):  
Rna Synthesis ◽  
Genomic Stability ◽  
Dna And Rna ◽  
Dna And Rna Synthesis

Critical role of the POT1 OB domain in maintaining genomic stability

Oncogene ◽  
2016 ◽  
Vol 36 (14) ◽  
pp. 1908-1910 ◽  
Author(s):  
T K Pandita
Keyword(s):  
Critical Role ◽  
Genomic Stability
Sign in / Sign up

Export Citation Format

Share Document