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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 24, 2022 |
| Title |
MDC1 maintains active elongation complexes of RNA polymerase II |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| 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.
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| 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.
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| Contributor(s) |
Pappas G, Thomas Q, Gregersen LH, Galanos P, Bartek J |
| Citation(s) |
36640322 |
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| Submission date |
Oct 18, 2022 |
| Last update date |
Feb 23, 2023 |
| Contact name |
Lea Haarup Gregersen |
| E-mail(s) |
leag@sund.ku.dk
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| Phone |
31241987
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| Organization name |
University of Copenhagen
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| Department |
ICMM
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| Street address |
Blegdamsvej 3B,
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| City |
København |
| ZIP/Postal code |
2200 |
| Country |
Denmark |
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| Platforms (1) |
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| Samples (16)
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| 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 |
| GSM6652459 |
U2OS siMDC1 replicate 2, DRB, 10 min release |
| GSM6652460 |
U2OS siControl replicate 1, DRB, 20 min release |
| GSM6652461 |
U2OS siMDC1 replicate 1, DRB, 20 min release |
| GSM6652462 |
U2OS siControl replicate 2, DRB, 20 min release |
| GSM6652463 |
U2OS siMDC1 replicate 2, DRB, 20 min release |
| GSM6652464 |
U2OS siControl replicate 1, DRB, 30 min release |
| GSM6652465 |
U2OS siMDC1 replicate 1, DRB, 30 min release |
| GSM6652466 |
U2OS siControl replicate 2, DRB, 30 min release |
| GSM6652467 |
U2OS siMDC1 replicate 2, DRB, 30 min release |
| GSM6652468 |
U2OS siControl replicate 1, DRB, 40 min release |
| GSM6652469 |
U2OS siMDC1 replicate 1, DRB, 40 min release |
| GSM6652470 |
U2OS siControl replicate 2, DRB, 40 min release |
| GSM6652471 |
U2OS siMDC1 replicate 2, DRB, 40 min release |
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| Relations |
| BioProject |
PRJNA891669 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE215990_RAW.tar |
832.7 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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