A unique hypofractionated radiotherapy schedule with 51.3 Gy in 18 fractions three times per week for early breast cancer: outcomes including local control, acute and late skin toxicity

Kouloulias, Vassilis; Gogalis, J.; Zygogianni, Anna; Armpilia, Christina; Antypas, Christos; John, K.; Porfyrios, Koromperlis; Gennimata, Vasiliki; Kouvaris, John

doi:10.1007/s12282-016-0697-0

Cited by 6 publications

(3 citation statements)

References 30 publications

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“…We were now searching for a mechanism that allows the ISR to interfere with DNA replication. DNA:RNA hybrids (R-loops) have recently emerged as one of the major players in regulating DNA replication 15,17,35 . They are formed through the hybridization of newly synthesized RNA to its template DNA while looping out the opposite DNA strand.…”

Section: Stimulation Of the Isr Induces R-loopsmentioning

confidence: 99%

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The integrated stress response induces R-loops and hinders replication fork progression

et al. 2020

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The integrated stress response (ISR) allows cells to rapidly shutdown most of their protein synthesis in response to protein misfolding, amino acid deficiency, or virus infection. These stresses trigger the phosphorylation of the translation initiation factor eIF2alpha, which prevents the initiation of translation. Here we show that triggering the ISR drastically reduces the progression of DNA replication forks within 1 h, thus flanking the shutdown of protein synthesis with immediate inhibition of DNA synthesis. DNA replication is restored by compounds that inhibit eIF2alpha kinases or re-activate eIF2alpha. Mechanistically, the translational shutdown blocks histone synthesis, promoting the formation of DNA:RNA hybrids (R-loops), which interfere with DNA replication. R-loops accumulate upon histone depletion. Conversely, histone overexpression or R-loop removal by RNaseH1 each restores DNA replication in the context of ISR and histone depletion. In conclusion, the ISR rapidly stalls DNA synthesis through histone deficiency and R-loop formation. We propose that this shutdown mechanism prevents potentially detrimental DNA replication in the face of cellular stresses.

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Section: Stimulation Of the Isr Induces R-loopsmentioning

confidence: 99%

“…Finally, replication stress can be induced by the formation of Rloops, i.e., DNA:RNA hybrids that form by the looping out of the non-template strand of DNA after transcription, allowing the newly synthesized RNA to rehybridize with its template strand 14,15 . Such R-loops represent obstacles to DNA replication [16][17][18][19][20] .…”

Section: Introductionmentioning

confidence: 99%

The integrated stress response induces R-loops and hinders replication fork progression

et al. 2020

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“…Vassilis et al [19] untersuchten 80 Patientinnen bezüglich lokaler Kontrolle, Fernmetastasierung, Akut-und Spätnebenwirkungen sowie kosmetischem Ergebnis nach 42,75 Gy in 15 Fraktionen über 5 Wochen nach 3 Jahren und fanden vergleichbar gute Ergebnisse zu den publizierten Daten zur normofraktionierten Ganzbrustbestrahlung.…”

Section: Die Early Breast Cancer Trialists Collaborative Groupunclassified