EGFR inhibits DNA mismatch repair

Hsieh, Peggy; Pearlman, Alexander H.

doi:10.1073/pnas.1505168112

Cited by 4 publications

(3 citation statements)

References 18 publications

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“…The mobilization of ErbB receptor dimers and gap junctions interfere in several ways. Nuclear DNA injury releases signaling factors like HSPs and ARPs [ 28 , 57 ] which target not only Erb receptor dimers and induce caveolin and importin-

dependent nucleograde transport [ 58 , 59 ], but also affect the retrograde trafficking of gap junctions [ 60 , 61 , 62 ]. This initiates transport routes which guide internalized and vesicle-packed gap junctions towards the perinuclear cytosol by utilizing structural, functional, and regulation components of the regular retrograde trafficking machinery.…”

Section: Introductionmentioning

confidence: 99%

Localisation Microscopy of Breast Epithelial ErbB-2 Receptors and Gap Junctions: Trafficking after γ-Irradiation, Neuregulin-1β, and Trastuzumab Application

Pilarczyk

Nesnidal

Gunkel

et al. 2017

IJMS

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In cancer, vulnerable breast epithelium malignance tendency correlates with number and activation of ErbB receptor tyrosine kinases. In the presented work, we observe ErbB receptors activated by irradiation-induced DNA injury or neuregulin-1sans-serifβ application, or alternatively, attenuated by a therapeutic antibody using high resolution fluorescence localization microscopy. The gap junction turnover coinciding with ErbB receptor activation and co-transport is simultaneously recorded. DNA injury caused by 4 Gray of 6 MeV photon γ-irradiation or alternatively neuregulin-1sans-serifβ application mobilized ErbB receptors in a nucleograde fashion—a process attenuated by trastuzumab antibody application. This was accompanied by increased receptor density, indicating packing into transport units. Factors mobilizing ErbB receptors also mobilized plasma membrane resident gap junction channels. The time course of ErbB receptor activation and gap junction mobilization recapitulates the time course of non-homologous end-joining DNA repair. We explain our findings under terms of DNA injury-induced membrane receptor tyrosine kinase activation and retrograde trafficking. In addition, we interpret the phenomenon of retrograde co-trafficking of gap junction connexons stimulated by ErbB receptor activation.

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Section: Introductionmentioning

confidence: 99%

Localisation Microscopy of Breast Epithelial ErbB-2 Receptors and Gap Junctions: Trafficking after γ-Irradiation, Neuregulin-1β, and Trastuzumab Application

Pilarczyk

Nesnidal

Gunkel

et al. 2017

IJMS

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“…Mammalian cells have evolved sophisticated DNA repair systems to correct mispaired or damaged bases and extrahelical loops. In the mismatch repair (MMR) pathway, MutS-like heterodimers (MutSα, MSH2–MSH6 and MutSβ, MSH2–MSH3) recognize chemically modified or extrahelical DNA, and initiate sequential assembly of downstream repair machinery to repair the lesion 1 2 3 . Surprisingly, however, the eukaryotic mismatch recognition complex, MSH2–MSH3, not only fails to act as a guardian of the genome at the long disease-length trinucleotide repeat (TNR) tracts but also causes expansion, the lethal mutation underlying Huntington's disease (HD) as well as at least 30 other fatal diseases 4 5 6 7 8 .…”

mentioning

confidence: 99%

Crosstalk between MSH2–MSH3 and polβ promotes trinucleotide repeat expansion during base excision repair

et al. 2016

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Studies in knockout mice provide evidence that MSH2–MSH3 and the BER machinery promote trinucleotide repeat (TNR) expansion, yet how these two different repair pathways cause the mutation is unknown. Here we report the first molecular crosstalk mechanism, in which MSH2–MSH3 is used as a component of the BER machinery to cause expansion. On its own, pol β fails to copy TNRs during DNA synthesis, and bypasses them on the template strand to cause deletion. Remarkably, MSH2–MSH3 not only stimulates pol β to copy through the repeats but also enhances formation of the flap precursor for expansion. Our results provide direct evidence that MMR and BER, operating together, form a novel hybrid pathway that changes the outcome of TNR instability from deletion to expansion during the removal of oxidized bases. We propose that cells implement crosstalk strategies and share machinery when a canonical pathway is ineffective in removing a difficult lesion.

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“…In summary, this novel study provides evidence that PCNA-Y211p may be more abundant in EGFR-expressing cancer cells, and this may lower the efficiency of MMR, compounding other factors that deregulate genome maintenance and/or cell growth control in EGFR-positive human cancer cells. This study suggests a novel mechanism by which post-translational modification of replicative factor PCNA could lead to increased mutation rate and/or cancer progression [79, 80]. Additional in vivo and clinical studies are needed to explore the implications of this result.…”

Section: Pcna Tyrosine Phosphorylation In Cancer Cells Alters Its Funmentioning

confidence: 99%

Regulation of mismatch repair by histone code and posttranslational modifications in eukaryotic cells

Ortega

et al. 2016

DNA Repair

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DNA mismatch repair (MMR) protects genome integrity by correcting DNA replication-associated mispairs, modulating DNA damage-induced cell cycle checkpoints and regulating homeologous recombination. Loss of MMR function leads to cancer development. This review describes progress in understanding how MMR is carried out in the context of chromatin and how chromatin organization/compaction, epigenetic mechanisms and posttranslational modifications of MMR proteins influence and regulate MMR in eukaryotic cells.

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EGFR inhibits DNA mismatch repair

Cited by 4 publications

References 18 publications

Localisation Microscopy of Breast Epithelial ErbB-2 Receptors and Gap Junctions: Trafficking after γ-Irradiation, Neuregulin-1β, and Trastuzumab Application

Localisation Microscopy of Breast Epithelial ErbB-2 Receptors and Gap Junctions: Trafficking after γ-Irradiation, Neuregulin-1β, and Trastuzumab Application

Crosstalk between MSH2–MSH3 and polβ promotes trinucleotide repeat expansion during base excision repair

Regulation of mismatch repair by histone code and posttranslational modifications in eukaryotic cells

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