LC8/DYNLL1 is a 53BP1 effector and regulates checkpoint activation

West, Kirk; Kelliher, Jessica L.; Xu, Zhanzhan; An, Liwei; Reed, Megan R.; Eoff, Robert L.; Wang, Jiadong; Huen, Michael S.Y.; Leung, Justin

doi:10.1093/nar/gkz263

Cited by 38 publications

(34 citation statements)

References 75 publications

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“…The existence of epigenetic memory seems to be crucial in the process of adaptation to new conditions. DYNLL1 gene was repeatedly linked with DNA repair processes, especially as an effector in non-homologous end joining (NHEJ) repair [46]. DNA methylation decrease in DYNLL1 gene in a CpG island found in exposed subjects in our study could be the reason for intensive NHEJ repair processes in this group.…”

Section: Discussionmentioning

confidence: 51%

DNA Methylation Profiles in a Group of Workers Occupationally Exposed to Nanoparticles

Rössnerová

Hoňková

Pelclová

et al. 2020

IJMS

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The risk of exposure to nanoparticles (NPs) has rapidly increased during the last decade due to the vast use of nanomaterials (NMs) in many areas of human life. Despite this fact, human biomonitoring studies focused on the effect of NP exposure on DNA alterations are still rare. Furthermore, there are virtually no epigenetic data available. In this study, we investigated global and gene-specific DNA methylation profiles in a group of 20 long-term (mean 14.5 years) exposed, nanocomposite, research workers and in 20 controls. Both groups were sampled twice/day (pre-shift and post-shift) in September 2018. We applied Infinium Methylation Assay, using the Infinium MethylationEPIC BeadChips with more than 850,000 CpG loci, for identification of the DNA methylation pattern in the studied groups. Aerosol exposure monitoring, including two nanosized fractions, was also performed as proof of acute NP exposure. The obtained array data showed significant differences in methylation between the exposed and control groups related to long-term exposure, specifically 341 CpG loci were hypomethylated and 364 hypermethylated. The most significant CpG differences were mainly detected in genes involved in lipid metabolism, the immune system, lung functions, signaling pathways, cancer development and xenobiotic detoxification. In contrast, short-term acute NP exposure was not accompanied by DNA methylation changes. In summary, long-term (years) exposure to NP is associated with DNA epigenetic alterations.

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Section: Discussionmentioning

confidence: 51%

DNA Methylation Profiles in a Group of Workers Occupationally Exposed to Nanoparticles

Rössnerová

Hoňková

Pelclová

et al. 2020

IJMS

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“…When DNA damage occurs within 6 hr, a change in the phosphorylation level of H2A.X can be detected. 9,43 Conclusion U2-AuNP shows outstanding inhibition of GBM in vitro and in vivo. Based on our previous research, we found that the U2-AuNP complex exhibits potential value as a multifunctional therapeutic strategy for inhibiting the EGFR-related pathway and preventing DNA damage repair to GBM.…”

Section: Discussionmentioning

confidence: 97%

<p>Aptamer-Conjugated Gold Nanoparticles Targeting Epidermal Growth Factor Receptor Variant III for the Treatment of Glioblastoma</p>

Peng¹,

Liang²,

Zhong³

et al. 2020

IJN

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In this study, we constructed novel brain-targeting complexes (U2-AuNP) by conjugating aptamer U2 to the gold nanoparticle (AuNPs) surface as a promising option for GBM therapy. Materials and Methods: The properties of the U2-AuNP complexes were thoroughly characterized. Then, we detected the in vitro effects of U2-AuNP in U87-EGFRvIII cell lines and the in vivo antitumor effects of U2-AuNP in GBM-bearing mice. Furthermore, we explored the inhibition mechanism of U2-AuNP in U87-EGFRvIII cell lines. Results: We found that U2-AuNP inhibits the proliferation and invasion of U87-EGFRvIII cell lines and prolongs the survival time of GBM-bearing mice. We found that U2-AuNP can inhibit the EGFR-related pathway and prevent DNA damage repair in GBM cells. Conclusion: These results reveal the promising potential of U2-AuNP as a drug candidate for targeted therapy in GBM.

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“…Transfections were carried out using both Polyethylenimine (PEI) (Polysciences, Inc.) and FuGene HD (Promega) according to the manufacturer's instruction. U2OS RNF168 KO cells 56 were generated using CRISPR/Cas9 method. RNF168 gRNA1-GCATAAACTCGCCTTTTCGA and gRNA2-GGAAGTGGGT GAGTAACCA were cloned into pSpCas9(BB)-2A-Puro (a gift from Fen Zhang-Addgene ID: 48139).…”

Section: Methodsmentioning

confidence: 99%

Histone H2A variants alpha1-extension helix directs RNF168-mediated ubiquitination

et al. 2020

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Histone ubiquitination plays an important role in the DNA damage response (DDR) pathway. RNF168 catalyzes H2A and H2AX ubiquitination on lysine 13/15 (K13/K15) upon DNA damage and promotes the accrual of downstream repair factors at damaged chromatin. Here, we report that RNF168 ubiquitinates the non-canonical H2A variants H2AZ and macroH2A1/ 2 at the divergent N-terminal tail lysine residue. In addition to their evolutionarily conserved nucleosome acidic patch, we identify the positively charged alpha1-extension helix as essential for RNF168-mediated ubiquitination of H2A variants. Moreover, mutation of the RNF168 UMI (UIM-and MIU-related UBD) hydrophilic acidic residues abolishes RNF168mediated ubiquitination as well as 53BP1 and BRCA1 ionizing radiation-induced foci formation. Our results reveal a juxtaposed bipartite electrostatic interaction utilized by the nucleosome to direct RNF168 orientation towards the target lysine residues in proximity to the H2A alpha1-extension helix, which plays an important role in the DDR pathway.

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LC8/DYNLL1 is a 53BP1 effector and regulates checkpoint activation

Cited by 38 publications

References 75 publications

DNA Methylation Profiles in a Group of Workers Occupationally Exposed to Nanoparticles

DNA Methylation Profiles in a Group of Workers Occupationally Exposed to Nanoparticles

<p>Aptamer-Conjugated Gold Nanoparticles Targeting Epidermal Growth Factor Receptor Variant III for the Treatment of Glioblastoma</p>

Histone H2A variants alpha1-extension helix directs RNF168-mediated ubiquitination

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