MDC1 maintains active elongation complexes of RNA polymerase II

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Standard

MDC1 maintains active elongation complexes of RNA polymerase II. / Pappas, George; Munk, Sebastian Howen Nesgaard; Watanabe, Kenji; Thomas, Quentin; Gál, Zita; Gram, Helena Hagner; Lee, Myung Hee; Gómez-Cabello, Daniel; Kanellis, Dimitris Christos; Olivares-Chauvet, Pedro; Larsen, Dorthe Helena; Gregersen, Lea Haarup; Maya-Mendoza, Apolinar; Galanos, Panagiotis; Bartek, Jiri.

I: Cell Reports, Bind 42, Nr. 1, 111979, 2023.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Pappas, G, Munk, SHN, Watanabe, K, Thomas, Q, Gál, Z, Gram, HH, Lee, MH, Gómez-Cabello, D, Kanellis, DC, Olivares-Chauvet, P, Larsen, DH, Gregersen, LH, Maya-Mendoza, A, Galanos, P & Bartek, J 2023, 'MDC1 maintains active elongation complexes of RNA polymerase II', Cell Reports, bind 42, nr. 1, 111979. https://doi.org/10.1016/j.celrep.2022.111979

APA

Pappas, G., Munk, S. H. N., Watanabe, K., Thomas, Q., Gál, Z., Gram, H. H., Lee, M. H., Gómez-Cabello, D., Kanellis, D. C., Olivares-Chauvet, P., Larsen, D. H., Gregersen, L. H., Maya-Mendoza, A., Galanos, P., & Bartek, J. (2023). MDC1 maintains active elongation complexes of RNA polymerase II. Cell Reports, 42(1), [111979]. https://doi.org/10.1016/j.celrep.2022.111979

Vancouver

Pappas G, Munk SHN, Watanabe K, Thomas Q, Gál Z, Gram HH o.a. MDC1 maintains active elongation complexes of RNA polymerase II. Cell Reports. 2023;42(1). 111979. https://doi.org/10.1016/j.celrep.2022.111979

Author

Pappas, George ; Munk, Sebastian Howen Nesgaard ; Watanabe, Kenji ; Thomas, Quentin ; Gál, Zita ; Gram, Helena Hagner ; Lee, Myung Hee ; Gómez-Cabello, Daniel ; Kanellis, Dimitris Christos ; Olivares-Chauvet, Pedro ; Larsen, Dorthe Helena ; Gregersen, Lea Haarup ; Maya-Mendoza, Apolinar ; Galanos, Panagiotis ; Bartek, Jiri. / MDC1 maintains active elongation complexes of RNA polymerase II. I: Cell Reports. 2023 ; Bind 42, Nr. 1.

Bibtex

@article{c850671927074fd5801218332fe73f7f,

title = "MDC1 maintains active elongation complexes of RNA polymerase II",

abstract = "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 the role of MDC1 in transcription as a regulator of RNA polymerase II (RNAPII). Depletion of MDC1 causes a genome-wide reduction in the abundance of actively engaged RNAPII elongation complexes throughout the gene body of protein-encoding genes under unperturbed conditions. Decreased engaged RNAPII subsequently alters the assembly of the spliceosome complex on chromatin, leading to changes 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 role of MDC1 in RNAPII-mediated transcription with potential implications for cancer treatment.",

keywords = "cancer, CP: Molecular biology, DNA double-strand breaks, MDC1, pre-mRNA splicing, RNA polymerase II, transcription elongation",

author = "George Pappas and Munk, {Sebastian Howen Nesgaard} and Kenji Watanabe and Quentin Thomas and Zita G{\'a}l and Gram, {Helena Hagner} and Lee, {Myung Hee} and Daniel G{\'o}mez-Cabello and Kanellis, {Dimitris Christos} and Pedro Olivares-Chauvet and Larsen, {Dorthe Helena} and Gregersen, {Lea Haarup} and Apolinar Maya-Mendoza and Panagiotis Galanos and Jiri Bartek",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

doi = "10.1016/j.celrep.2022.111979",

language = "English",

volume = "42",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "1",

}

RIS

TY - JOUR

T1 - MDC1 maintains active elongation complexes of RNA polymerase II

AU - Pappas, George

AU - Munk, Sebastian Howen Nesgaard

AU - Watanabe, Kenji

AU - Thomas, Quentin

AU - Gál, Zita

AU - Gram, Helena Hagner

AU - Lee, Myung Hee

AU - Gómez-Cabello, Daniel

AU - Kanellis, Dimitris Christos

AU - Olivares-Chauvet, Pedro

AU - Larsen, Dorthe Helena

AU - Gregersen, Lea Haarup

AU - Maya-Mendoza, Apolinar

AU - Galanos, Panagiotis

AU - Bartek, Jiri

PY - 2023

Y1 - 2023

N2 - 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 the role of MDC1 in transcription as a regulator of RNA polymerase II (RNAPII). Depletion of MDC1 causes a genome-wide reduction in the abundance of actively engaged RNAPII elongation complexes throughout the gene body of protein-encoding genes under unperturbed conditions. Decreased engaged RNAPII subsequently alters the assembly of the spliceosome complex on chromatin, leading to changes 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 role of MDC1 in RNAPII-mediated transcription with potential implications for cancer treatment.

AB - 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 the role of MDC1 in transcription as a regulator of RNA polymerase II (RNAPII). Depletion of MDC1 causes a genome-wide reduction in the abundance of actively engaged RNAPII elongation complexes throughout the gene body of protein-encoding genes under unperturbed conditions. Decreased engaged RNAPII subsequently alters the assembly of the spliceosome complex on chromatin, leading to changes 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 role of MDC1 in RNAPII-mediated transcription with potential implications for cancer treatment.

KW - cancer

KW - CP: Molecular biology

KW - DNA double-strand breaks

KW - MDC1

KW - pre-mRNA splicing

KW - RNA polymerase II

KW - transcription elongation

U2 - 10.1016/j.celrep.2022.111979

DO - 10.1016/j.celrep.2022.111979

M3 - Journal article

C2 - 36640322

AN - SCOPUS:85147106239

VL - 42

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 1

M1 - 111979

ER -

ID: 336769794