Caught with One's Zinc Fingers in the Genome Integrity Cookie Jar

Vilas, Caroline K.; Emery, Lara E.; Denchi, Eros Lazzerini; Miller, Kyle M.

doi:10.1016/j.tig.2017.12.011

Cited by 56 publications

(47 citation statements)

References 108 publications

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“…Many zinc finger proteins (ZFPs) such as ZFHX3, ZN292, ZN296, ZN462, and ZN703 also showed higher representation in HLNRA individuals. Zinc finger domain is one of the most abundant DNA-binding motifs found in eukaryotic transcriptional factors and several ZFPs have been implicated in telomere maintenance, signal transduction and DNA repair 32 . Chromatin is now considered a dynamic participant in all processes that use DNA as the template to facilitate, regulate or terminate cellular responses.…”

Section: Resultsmentioning

confidence: 99%

Chronic exposure of humans to high level natural background radiation leads to robust expression of protective stress response proteins

Nishad

Chauhan

Sowdhamini

et al. 2021

Sci Rep

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Understanding exposures to low doses of ionizing radiation are relevant since most environmental, diagnostic radiology and occupational exposures lie in this region. However, the molecular mechanisms that drive cellular responses at these doses, and the subsequent health outcomes, remain unclear. A local monazite-rich high level natural radiation area (HLNRA) in the state of Kerala on the south-west coast of Indian subcontinent show radiation doses extending from ≤ 1 to ≥ 45 mGy/y and thus, serve as a model resource to understand low dose mechanisms directly on healthy humans. We performed quantitative discovery proteomics based on multiplexed isobaric tags (iTRAQ) coupled with LC–MS/MS on human peripheral blood mononuclear cells from HLNRA individuals. Several proteins involved in diverse biological processes such as DNA repair, RNA processing, chromatin modifications and cytoskeletal organization showed distinct expression in HLNRA individuals, suggestive of both recovery and adaptation to low dose radiation. In protein–protein interaction (PPI) networks, YWHAZ (14-3-3ζ) emerged as the top-most hub protein that may direct phosphorylation driven pro-survival cellular processes against radiation stress. PPI networks also identified an integral role for the cytoskeletal protein ACTB, signaling protein PRKACA; and the molecular chaperone HSPA8. The data will allow better integration of radiation biology and epidemiology for risk assessment [Data are available via ProteomeXchange with identifier PXD022380].

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Section: Resultsmentioning

confidence: 99%

Chronic exposure of humans to high level natural background radiation leads to robust expression of protective stress response proteins

Nishad

Chauhan

Sowdhamini

et al. 2021

Sci Rep

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“…These included highly expressed TFs in young LEPs that were down-regulated with age, such as: ELF5, GRHL2 ( Figure S3Hi), HES4 ( Figure S3Hii), SGSM2 ( Figure S3Hiii), SOX4, TEAD2, ZNF641, ZNF827 ( Figure 3Hi), and genome organizer SATB1 (Figure 3Hii). ZNF827 mediates telomere homeostasis through recruitment of DNA repair proteins [Vilas et al, 2018]. Loss of GRHL2 and SGSM2 are associated with down-regulation of E-cadherin and epithelial-to-mesenchymal transition (EMT) in mammary epithelial cells [Xiang et al, 2012, Lin et al, 2019.…”

Section: These Molecular Changes Recapitulated Previous Phenotypic Obmentioning

confidence: 99%

Epigenetic changes with age primes mammary luminal epithelia for cancer initiation

Sayaman

Miyano

Senapati

et al. 2021

Preprint

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Aging causes molecular changes that manifest as stereotypical phenotypes yet aging-associated diseases progress only in certain individuals. At lineage-specific resolution, we show how stereotyped and variant responses are integrated in mammary epithelia. Age-dependent directional changes in gene expression and DNA methylation (DNAm) occurred almost exclusively in luminal cells and implicated genome organizers SATB1 and CTCF. DNAm changes were robust indicators of aging luminal cells, and were either directly (anti-)correlated with expression changes or served as priming events for subsequent dysregulation, such as demethylation of ESR1-binding regions in DNAm-regulatory CXXC5 in older luminal cells and luminal-subtype cancers. Variance-driven changes in the transcriptome of both luminal and myoepithelial lineages further contributed to age-dependent loss of lineage fidelity. The pathways affected by transcriptomic and DNAm changes during aging are commonly linked with breast cancer, and together with the differential variability found across individuals, influence aging-associated cancer susceptibility in a subtype-specific manner.

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“…Proteins possessing zinc finger domain potentially bind to DNA, which may be involved in various cellular processes such as transcription regulation, DNA modification, and DNA damage repair. Multiple zinc finger proteins are reported to be involved in DNA damage response such as BRCA1, PARP1, and ZMYM3 27 . We are interested in identifying zinc finger proteins that have not been previously studied in the DNA damage response.…”

Section: Resultsmentioning

confidence: 99%

ZFP161 regulates replication fork stability and maintenance of genomic stability by recruiting the ATR/ATRIP complex

Kim

Zhao

et al. 2019

Nat Commun

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DNA replication stress-mediated activation of the ATR kinase pathway is important for maintaining genomic stability. In this study, we identified a zinc finger protein, ZFP161 that functions as a replication stress response factor in ATR activation. Mechanistically, ZFP161 acts as a scaffolding protein to facilitate the interaction between RPA and ATR/ATRIP. ZFP161 binds to RPA and ATR/ATRIP through distinct regions and stabilizes the RPA–ATR–ATRIP complex at stalled replication forks. This function of ZFP161 is important to the ATR signaling cascade and genome stability maintenance. In addition, ZFP161 knockout mice showed a defect in ATR activation and genomic instability. Furthermore, low expression of ZFP161 is associated with higher cancer risk and chromosomal instability. Overall, these findings suggest that ZFP161 coordinates ATR/Chk1 pathway activation and helps maintain genomic stability.

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Caught with One's Zinc Fingers in the Genome Integrity Cookie Jar

Cited by 56 publications

References 108 publications

Chronic exposure of humans to high level natural background radiation leads to robust expression of protective stress response proteins

Chronic exposure of humans to high level natural background radiation leads to robust expression of protective stress response proteins

Epigenetic changes with age primes mammary luminal epithelia for cancer initiation

ZFP161 regulates replication fork stability and maintenance of genomic stability by recruiting the ATR/ATRIP complex

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