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Series GSE205583 Query DataSets for GSE205583
Status Public on Sep 07, 2022
Title Multimerization of MYC shields stalled replication forks from RNA polymerase [BLISS]
Organism Homo sapiens
Experiment type Other
Summary Oncoproteins of the MYC family drive the development of numerous human tumors. In unperturbed cells, MYC proteins bind to virtually all active promoters and control transcription by RNA Polymerase II (RNAPII). MYC proteins can also coordinate transcription with DNA replication and promote the repair of transcription-associated DNA damage, but how they exert these mechanistically diverse functions is unknown. Here we show that MYC dissociates from many of its binding sites in active promoters and forms multimeric, often sphere-like structures in response to perturbation of transcription elongation, mRNA splicing or inhibition of the proteasome. Multimerization is accompanied by a global change in the MYC interactome towards proteins involved in transcription termination and RNA processing. MYC multimers accumulate on chromatin immediately adjacent to stalled replication forks and surround FANCD2, ATR and BRCA1 proteins, which are located at stalled forks. MYC multimerization is triggered in a HUWE1 and ubiquitylation-dependent manner. At active promoters, MYC multimers block antisense transcription and stabilize FANCD2 association with chromatin. This limits DNA double-strand break formation during S-phase and allows rapid recovery from replication stress, suggesting that multimerization of MYC enables tumor cells to proliferate under stressful conditions
 
Overall design Sequencing of double-strand breaks in cells exposed to HU, BI8626 in presence or absence of MYC induction
 
Contributor(s) Solvie D, Baluapuri A, Uhl L, Endres T, Wolf E, Eilers M
Citation(s) 36424410
Submission date Jun 07, 2022
Last update date Dec 02, 2022
Contact name Martin Eilers
Organization name University of Wuerzburg
Department Chair for Biochemistry and Molecular Biology
Lab Martin Eilers
Street address Am Hubland
City Wuerzburg
ZIP/Postal code 97074
Country Germany
 
Platforms (1)
GPL30173 NextSeq 2000 (Homo sapiens)
Samples (12)
GSM6215138 BLISS HU rep1
GSM6215139 BLISS HU BI8626 rep1
GSM6215140 BLISS HU Dox rep1
This SubSeries is part of SuperSeries:
GSE205585 Multimerization of MYC shields stalled replication forks from RNA polymerase.
Relations
BioProject PRJNA846591

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Supplementary file Size Download File type/resource
GSE205583_RAW.tar 26.8 Mb (http)(custom) TAR (of BEDGRAPH)
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Raw data are available in SRA
Processed data provided as supplementary file

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