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Updated: Aug 20, 2025
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Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
Published on: April 29, 2010
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MYC multimers shield stalled replication forks from RNA polymerase.
Daniel Solvie1, Apoorva Baluapuri1,2,3, Leonie Uhl1
1Department of Biochemistry and Molecular Biology, University of Würzburg, Würzburg, Germany.
Nature
|November 24, 2022
Summary
MYC oncoproteins form structures that help cancer cells survive stress by coordinating DNA repair and replication, limiting DNA damage during S-phase.
Area of Science:
- Molecular Biology
- Cancer Biology
- Cellular Stress Response
Background:
- MYC oncoproteins are crucial drivers of human tumor development.
- MYC proteins regulate transcription, DNA replication, and DNA damage repair in normal cells.
Purpose of the Study:
- To elucidate the mechanisms behind MYC's diverse cellular functions.
- To investigate the structural changes and functional consequences of MYC perturbation.
Main Methods:
- Analysis of MYC protein behavior upon perturbation of transcription elongation, mRNA splicing, and proteasome inhibition.
- Characterization of MYC interactome changes and multimer formation.
- Localization studies of MYC multimers in relation to stalled replication forks and DNA repair proteins (FANCD2, ATR, BRCA1).
Main Results:
- MYC dissociates from promoters and forms multimeric structures under cellular stress.
- MYC multimerization alters its interactome towards transcription termination and RNA processing factors.
- MYC multimers accumulate near stalled replication forks, interacting with DNA repair proteins and blocking antisense transcription.
Conclusions:
- MYC multimerization is a ubiquitylation-dependent process triggered by cellular stress.
- MYC multimers stabilize DNA repair proteins at stalled replication forks, limiting DNA double-strand breaks.
- MYC multimerization is a key mechanism enabling tumor cell proliferation under stressful conditions.
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