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Series GSE215990 Query DataSets for GSE215990
Status Public on Nov 24, 2022
Title MDC1 maintains active elongation complexes of RNA polymerase II
Organism Homo sapiens
Experiment type Other
Summary The role of MDC1 in the DNA damage response has been extensively studied, however, its impact on other cellular processes is not well understood. Here, we describe a role for MDC1 in transcription by regulating the activity of the RNAPolymerase II (RNAPII). Depletion of MDC1 caused a genome-wide reduction in the abundance of actively engaged RNAPII elongation complexes throughout the gene body of protein coding genes under unperturbed conditions. Decreased engaged RNAPII subsequently alters the assembly of the spliceosome complex on chromatin, leading to defects in pre-mRNA splicing. Mechanistically, the S/TQ domain of MDC1 modulates RNAPII-mediated transcription. Upon genotoxic stress, MDC1 promotes the abundance of engaged RNAPII complexes at DNA breaks, thereby stimulating nascent transcription at the damaged sites. Of clinical relevance, cancer cells lacking MDC1 display hypersensitivity to RNAPII inhibitors. Overall, we unveil a previously uncharacterized role of MDC1 in RNAPII-mediated transcription with potential implications for cancer treatment.
 
Overall design To study the RNAPII elongation rate in control and siMDC1 treated cells we performed DRB/Ttchem-seq as desribed in Gregersen et al. 2020 Nature Protocols.
 
Contributor(s) Pappas G, Thomas Q, Gregersen LH, Galanos P, Bartek J
Citation(s) 36640322
Submission date Oct 18, 2022
Last update date Feb 23, 2023
Contact name Lea Haarup Gregersen
E-mail(s) leag@sund.ku.dk
Phone 31241987
Organization name University of Copenhagen
Department ICMM
Street address Blegdamsvej 3B,
City KĂžbenhavn
ZIP/Postal code 2200
Country Denmark
 
Platforms (1)
GPL30173 NextSeq 2000 (Homo sapiens)
Samples (16)
GSM6652456 U2OS siControl replicate 1, DRB, 10 min release
GSM6652457 U2OS siMDC1 replicate 1, DRB, 10 min release
GSM6652458 U2OS siControl replicate 2, DRB, 10 min release
Relations
BioProject PRJNA891669

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Supplementary file Size Download File type/resource
GSE215990_RAW.tar 832.7 Mb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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