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Human RTEL1 associates with Poldip3 to facilitate responses to replication stress and R-loop resolution

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Björkman, A, Johansen, SL, Lin, L, Schertzer, M, Kanellis, DC, Katsori, A-M, Christensen, ST, Luo, Y, Andersen, JS, Elsässer, SJ, Londono-Vallejo, A, Bartek, J & Schou, KB 2020, 'Human RTEL1 associates with Poldip3 to facilitate responses to replication stress and R-loop resolution', Genes & Development, vol. 34, no. 15-16, pp. 1065-1074. https://doi.org/10.1101/GAD.330050.119

APA

Björkman, A., Johansen, S. L., Lin, L., Schertzer, M., Kanellis, D. C., Katsori, A-M., Christensen, S. T., Luo, Y., Andersen, J. S., Elsässer, S. J., Londono-Vallejo, A., Bartek, J., & Schou, K. B. (2020). Human RTEL1 associates with Poldip3 to facilitate responses to replication stress and R-loop resolution. Genes & Development, 34(15-16), 1065-1074. https://doi.org/10.1101/GAD.330050.119

CBE

Björkman A, Johansen SL, Lin L, Schertzer M, Kanellis DC, Katsori A-M, Christensen ST, Luo Y, Andersen JS, Elsässer SJ, Londono-Vallejo A, Bartek J, Schou KB. 2020. Human RTEL1 associates with Poldip3 to facilitate responses to replication stress and R-loop resolution. Genes & Development. 34(15-16):1065-1074. https://doi.org/10.1101/GAD.330050.119

MLA

Vancouver

Björkman A, Johansen SL, Lin L, Schertzer M, Kanellis DC, Katsori A-M et al. Human RTEL1 associates with Poldip3 to facilitate responses to replication stress and R-loop resolution. Genes & Development. 2020 Aug 1;34(15-16):1065-1074. https://doi.org/10.1101/GAD.330050.119

Author

Björkman, Andrea ; Johansen, Søren L ; Lin, Lin ; Schertzer, Mike ; Kanellis, Dimitris C ; Katsori, Anna-Maria ; Christensen, Søren T ; Luo, Yonglun ; Andersen, Jens S ; Elsässer, Simon J ; Londono-Vallejo, Arturo ; Bartek, Jiri ; Schou, Kenneth B. / Human RTEL1 associates with Poldip3 to facilitate responses to replication stress and R-loop resolution. In: Genes & Development. 2020 ; Vol. 34, No. 15-16. pp. 1065-1074.

Bibtex

@article{b5bb552826c44f76a580b3d51ef91ae1,
title = "Human RTEL1 associates with Poldip3 to facilitate responses to replication stress and R-loop resolution",
abstract = "RTEL1 helicase is a component of DNA repair and telomere maintenance machineries. While RTEL1's role in DNA replication is emerging, how RTEL1 preserves genomic stability during replication remains elusive. Here we used a range of proteomic, biochemical, cell, and molecular biology and gene editing approaches to provide further insights into potential role(s) of RTEL1 in DNA replication and genome integrity maintenance. Our results from complementary human cell culture models established that RTEL1 and the Polδ subunit Poldip3 form a complex and are/function mutually dependent in chromatin binding after replication stress. Loss of RTEL1 and Poldip3 leads to marked R-loop accumulation that is confined to sites of active replication, enhances endogenous replication stress, and fuels ensuing genomic instability. The impact of depleting RTEL1 and Poldip3 is epistatic, consistent with our proposed concept of these two proteins operating in a shared pathway involved in DNA replication control under stress conditions. Overall, our data highlight a previously unsuspected role of RTEL1 and Poldip3 in R-loop suppression at genomic regions where transcription and replication intersect, with implications for human diseases including cancer.",
keywords = "DNA damage response, DNA repair, DNA:RNA hybrid, Dyskeratosis congenita, Helicase, Hoyeral-hreiderson syndrome, Poldip3, Polymerase δ, POLδ, R-loop, RTEL1, Telomere maintenance",
author = "Andrea Bj{\"o}rkman and Johansen, {S{\o}ren L} and Lin Lin and Mike Schertzer and Kanellis, {Dimitris C} and Anna-Maria Katsori and Christensen, {S{\o}ren T} and Yonglun Luo and Andersen, {Jens S} and Els{\"a}sser, {Simon J} and Arturo Londono-Vallejo and Jiri Bartek and Schou, {Kenneth B}",
note = "{\textcopyright} 2020 Bj{\"o}rkman et al.; Published by Cold Spring Harbor Laboratory Press.",
year = "2020",
month = aug,
day = "1",
doi = "10.1101/GAD.330050.119",
language = "English",
volume = "34",
pages = "1065--1074",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press Publications Department",
number = "15-16",

}

RIS

TY - JOUR

T1 - Human RTEL1 associates with Poldip3 to facilitate responses to replication stress and R-loop resolution

AU - Björkman, Andrea

AU - Johansen, Søren L

AU - Lin, Lin

AU - Schertzer, Mike

AU - Kanellis, Dimitris C

AU - Katsori, Anna-Maria

AU - Christensen, Søren T

AU - Luo, Yonglun

AU - Andersen, Jens S

AU - Elsässer, Simon J

AU - Londono-Vallejo, Arturo

AU - Bartek, Jiri

AU - Schou, Kenneth B

N1 - © 2020 Björkman et al.; Published by Cold Spring Harbor Laboratory Press.

PY - 2020/8/1

Y1 - 2020/8/1

N2 - RTEL1 helicase is a component of DNA repair and telomere maintenance machineries. While RTEL1's role in DNA replication is emerging, how RTEL1 preserves genomic stability during replication remains elusive. Here we used a range of proteomic, biochemical, cell, and molecular biology and gene editing approaches to provide further insights into potential role(s) of RTEL1 in DNA replication and genome integrity maintenance. Our results from complementary human cell culture models established that RTEL1 and the Polδ subunit Poldip3 form a complex and are/function mutually dependent in chromatin binding after replication stress. Loss of RTEL1 and Poldip3 leads to marked R-loop accumulation that is confined to sites of active replication, enhances endogenous replication stress, and fuels ensuing genomic instability. The impact of depleting RTEL1 and Poldip3 is epistatic, consistent with our proposed concept of these two proteins operating in a shared pathway involved in DNA replication control under stress conditions. Overall, our data highlight a previously unsuspected role of RTEL1 and Poldip3 in R-loop suppression at genomic regions where transcription and replication intersect, with implications for human diseases including cancer.

AB - RTEL1 helicase is a component of DNA repair and telomere maintenance machineries. While RTEL1's role in DNA replication is emerging, how RTEL1 preserves genomic stability during replication remains elusive. Here we used a range of proteomic, biochemical, cell, and molecular biology and gene editing approaches to provide further insights into potential role(s) of RTEL1 in DNA replication and genome integrity maintenance. Our results from complementary human cell culture models established that RTEL1 and the Polδ subunit Poldip3 form a complex and are/function mutually dependent in chromatin binding after replication stress. Loss of RTEL1 and Poldip3 leads to marked R-loop accumulation that is confined to sites of active replication, enhances endogenous replication stress, and fuels ensuing genomic instability. The impact of depleting RTEL1 and Poldip3 is epistatic, consistent with our proposed concept of these two proteins operating in a shared pathway involved in DNA replication control under stress conditions. Overall, our data highlight a previously unsuspected role of RTEL1 and Poldip3 in R-loop suppression at genomic regions where transcription and replication intersect, with implications for human diseases including cancer.

KW - DNA damage response

KW - DNA repair

KW - DNA:RNA hybrid

KW - Dyskeratosis congenita

KW - Helicase

KW - Hoyeral-hreiderson syndrome

KW - Poldip3

KW - Polymerase δ

KW - POLδ

KW - R-loop

KW - RTEL1

KW - Telomere maintenance

UR - http://www.scopus.com/inward/record.url?scp=85089127066&partnerID=8YFLogxK

U2 - 10.1101/GAD.330050.119

DO - 10.1101/GAD.330050.119

M3 - Journal article

C2 - 32561545

VL - 34

SP - 1065

EP - 1074

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 15-16

ER -

ID: 61380498