Transcriptional factor MAZ promotes cisplatin-induced DNA damage repair in lung adenocarcinoma by regulating NEIL3

Wang, Tao; Zhu, Xu; Wang, Kai; Li, Jianglun; Hu, Xiao; Lin, Peng; Zhang, Jian

doi:10.1016/j.pupt.2023.102217

Cited by 2 publications

(2 citation statements)

References 27 publications

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“…S 6C ), suggesting that IOX1 regulates PIF1 transcriptional expression, possibly in part by indirectly affecting MAZ expression. Previous study showed that MAZ promoted chemoresistance in lung adenocarcinoma cells by inhibiting DNA damage [ 30 ]. Here, we examined the expression of MAZ in NSCLC and found that MAZ was highly expressed in NSCLC compared with normal lung fibroblasts (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…MAZ, a transcription factor, has been shown to exhibit aberrant expression in various tumor types, playing a role in the regulation of tumor cell proliferation, migration, apoptosis, and autophagy [ 40 ]. In lung cancer, MAZ promotes cisplatin resistance in lung adenocarcinoma cells by inhibiting DNA damage [ 30 ]. In this study, we observed a decrease in the enrichment of MAZ in the distal intergenic region of PIF1 following IOX1 treatment to result the suppression of PIF1 expression.…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of demethylase by IOX1 modulates chromatin accessibility to enhance NSCLC radiation sensitivity through attenuated PIF1

Li,

Qin,

Tian

et al. 2023

Cell Death Dis

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Chromatin accessibility is a critical determinant of gene transcriptional expression and regulated by histones modification. However, the potential for manipulating chromatin accessibility to regulate radiation sensitivity remains unclear. Our findings demonstrated that the histone demethylase inhibitor, 5-carboxy-8-hydroxyquinoline (IOX1), could enhance the radiosensitivity of non-small cell lung cancer (NSCLC) in vitro and in vivo. Mechanistically, IOX1 treatment reduced chromatin accessibility in the promoter region of DNA damage repair genes, leading to decreased DNA repair efficiency and elevated DNA damage induced by γ irradiation. Notably, IOX1 treatment significantly reduced both chromatin accessibility and the transcription of phytochrome interacting factor 1 (PIF1), a key player in telomere maintenance. Inhibition of PIF1 delayed radiation-induced DNA and telomeric DNA damage repair, as well as increased radiosensitivity of NSCLC in vitro and in vivo. Further study indicated that the above process was regulated by a reduction of transcription factor myc-associated zinc finger protein (MAZ) binding to the distal intergenic region of the PIF1. Taken together, IOX1-mediated demethylase inactivation reduced chromatin accessibility, leading to elevated telomere damage which is partly due to PIF1 inhibition, thereby enhancing NSCLC radiosensitivity.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhibition of demethylase by IOX1 modulates chromatin accessibility to enhance NSCLC radiation sensitivity through attenuated PIF1

Li,

Qin,

Tian

et al. 2023

Cell Death Dis

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RAG1/2 induces double‐stranded DNA breaks at non‐Ig loci in the proximity of single sequence repeats in developing B cells

Ochodnicka‐Mackovicova,

Mokry,

Haagmans

et al. 2024

Eur J Immunol

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In developing B cells, V(D)J gene recombination is initiated by the RAG1/2 endonuclease complex, introducing double‐stranded DNA breaks (DSBs) in V, D, and J genes and resulting in the formation of the hypervariable parts of immunoglobulins (Ig). Persistent or aberrant RAG1/2 targeting is a potential threat to genome integrity. While RAG1 and RAG2 have been shown to bind various regions genome‐wide, the in vivo off‐target DNA damage instigated by RAG1/2 endonuclease remains less well understood. In the current study, we identified regions containing RAG1/2‐induced DNA breaks in mouse pre‐B cells on a genome‐wide scale using a global DNA DSB detection strategy. We detected 1489 putative RAG1/2‐dependent DSBs, most of which were located outside the Ig loci. DNA sequence motif analysis showed a specific enrichment of RAG1/2‐induced DNA DSBs at GA‐ and CA‐repeats and GC‐rich motifs. These findings provide further insights into RAG1/2 off‐target activity. The ability of RAG1/2 to introduce DSBs on the non‐Ig loci during the endogenous V(D)J recombination emphasizes its genotoxic potential in developing lymphocytes.

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Transcriptional factor MAZ promotes cisplatin-induced DNA damage repair in lung adenocarcinoma by regulating NEIL3

Cited by 2 publications

References 27 publications

Inhibition of demethylase by IOX1 modulates chromatin accessibility to enhance NSCLC radiation sensitivity through attenuated PIF1

Inhibition of demethylase by IOX1 modulates chromatin accessibility to enhance NSCLC radiation sensitivity through attenuated PIF1

RAG1/2 induces double‐stranded DNA breaks at non‐Ig loci in the proximity of single sequence repeats in developing B cells

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