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Mechanisms of R-loop-mediated DNA Replication Stress: From Basic Principles to Cancer Therapy

Public support

  • Provider

    Czech Science Foundation

  • Programme

  • Call for proposals

    SGA0202600003

  • Main participants

    Ústav experimentální medicíny AV ČR, v. v. i.

  • Contest type

    VS - Public tender

  • Contract ID

    26-22773M

Alternative language

  • Project name in Czech

    Mechanisms of R-loop-mediated DNA Replication Stress: From Basic Principles to Cancer Therapy

  • Annotation in Czech

    Unscheduled transcription-replication conflicts (TRCs) associated with R-loop formation are major sources of DNA replication stress and cancer development. Recent research indicates that increased oxidative stress amplifies R-loop formation and results in DNA replication stalling through PRDX2-driven replisome alterations and a replication slowdown. This significantly reshapes our understanding of R-loop formation and replication stress in cancer cells, paving the way for new studies on genome instability during tumor development. We aim to investigate the conditions that promote R-loop formation and persistent replication stalling and to explore stress tolerance pathways activated by replication stress and R-loop formation. Finally, the vulnerabilities of hypoxic cancer cells to TRC processing inhibition will be tested, both in 2D and 3D models. This project is expected to deepen our understanding of the oxidative stress and DNA replication stress interplay, potentially introducing new strategies for cancer treatment.

Scientific branches

  • R&D category

    ZV - Basic research

  • OECD FORD - main branch

    10608 - Biochemistry and molecular biology

  • OECD FORD - secondary branch

  • OECD FORD - another secondary branch

  • CEP - equivalent branches <br>(according to the <a href="http://www.vyzkum.cz/storage/att/E6EF7938F0E854BAE520AC119FB22E8D/Prevodnik_oboru_Frascati.pdf">converter</a>)

    CE - Biochemistry<br>EB - Genetics and molecular biology

Solution timeline

  • Realization period - beginning

    Jan 1, 2026

  • Realization period - end

    Dec 31, 2030

  • Project status

    Z - Beginning multi-year project

  • Latest support payment

Data delivery to CEP

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

  • Data delivery code

    CEP26-GA0-GM-R

  • Data delivery date

    Apr 27, 2026

Finance

  • Total approved costs

    24,998 thou. CZK

  • Public financial support

    24,998 thou. CZK

  • Other public sources

    0 thou. CZK

  • Non public and foreign sources

    0 thou. CZK