Dynamic de novo heterochromatin assembly and disassembly at replication forks ensures fork stability

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Dynamic de novo heterochromatin assembly and disassembly at replication forks ensures fork stability. / Gaggioli, Vincent; Lo, Calvin S.Y.; Reverón-Gómez, Nazaret; Jasencakova, Zuzana; Domenech, Heura; Nguyen, Hong; Sidoli, Simone; Tvardovskiy, Andrey; Uruci, Sidrit; Slotman, Johan A.; Chai, Yi; Gonçalves, João G.S.C.Souto; Manolika, Eleni Maria; Jensen, Ole N.; Wheeler, David; Sridharan, Sriram; Chakrabarty, Sanjiban; Demmers, Jeroen; Kanaar, Roland; Groth, Anja; Taneja, Nitika.

In: Nature Cell Biology, Vol. 25, No. 7, 2023, p. 1017-1032.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Gaggioli, V, Lo, CSY, Reverón-Gómez, N, Jasencakova, Z, Domenech, H, Nguyen, H, Sidoli, S, Tvardovskiy, A, Uruci, S, Slotman, JA, Chai, Y, Gonçalves, JGSCS, Manolika, EM, Jensen, ON, Wheeler, D, Sridharan, S, Chakrabarty, S, Demmers, J, Kanaar, R, Groth, A & Taneja, N 2023, 'Dynamic de novo heterochromatin assembly and disassembly at replication forks ensures fork stability', Nature Cell Biology, vol. 25, no. 7, pp. 1017-1032. https://doi.org/10.1038/s41556-023-01167-z

APA

Gaggioli, V., Lo, C. S. Y., Reverón-Gómez, N., Jasencakova, Z., Domenech, H., Nguyen, H., Sidoli, S., Tvardovskiy, A., Uruci, S., Slotman, J. A., Chai, Y., Gonçalves, J. G. S. C. S., Manolika, E. M., Jensen, O. N., Wheeler, D., Sridharan, S., Chakrabarty, S., Demmers, J., Kanaar, R., ... Taneja, N. (2023). Dynamic de novo heterochromatin assembly and disassembly at replication forks ensures fork stability. Nature Cell Biology, 25(7), 1017-1032. https://doi.org/10.1038/s41556-023-01167-z

Vancouver

Gaggioli V, Lo CSY, Reverón-Gómez N, Jasencakova Z, Domenech H, Nguyen H et al. Dynamic de novo heterochromatin assembly and disassembly at replication forks ensures fork stability. Nature Cell Biology. 2023;25(7):1017-1032. https://doi.org/10.1038/s41556-023-01167-z

Author

Gaggioli, Vincent ; Lo, Calvin S.Y. ; Reverón-Gómez, Nazaret ; Jasencakova, Zuzana ; Domenech, Heura ; Nguyen, Hong ; Sidoli, Simone ; Tvardovskiy, Andrey ; Uruci, Sidrit ; Slotman, Johan A. ; Chai, Yi ; Gonçalves, João G.S.C.Souto ; Manolika, Eleni Maria ; Jensen, Ole N. ; Wheeler, David ; Sridharan, Sriram ; Chakrabarty, Sanjiban ; Demmers, Jeroen ; Kanaar, Roland ; Groth, Anja ; Taneja, Nitika. / Dynamic de novo heterochromatin assembly and disassembly at replication forks ensures fork stability. In: Nature Cell Biology. 2023 ; Vol. 25, No. 7. pp. 1017-1032.

Bibtex

@article{6e1feb892f3b42b0ac7e66631a0c2eed,
title = "Dynamic de novo heterochromatin assembly and disassembly at replication forks ensures fork stability",
abstract = "Chromatin is dynamically reorganized when DNA replication forks are challenged. However, the process of epigenetic reorganization and its implication for fork stability is poorly understood. Here we discover a checkpoint-regulated cascade of chromatin signalling that activates the histone methyltransferase EHMT2/G9a to catalyse heterochromatin assembly at stressed replication forks. Using biochemical and single molecule chromatin fibre approaches, we show that G9a together with SUV39h1 induces chromatin compaction by accumulating the repressive modifications, H3K9me1/me2/me3, in the vicinity of stressed replication forks. This closed conformation is also favoured by the G9a-dependent exclusion of the H3K9-demethylase JMJD1A/KDM3A, which facilitates heterochromatin disassembly upon fork restart. Untimely heterochromatin disassembly from stressed forks by KDM3A enables PRIMPOL access, triggering single-stranded DNA gap formation and sensitizing cells towards chemotherapeutic drugs. These findings may help in explaining chemotherapy resistance and poor prognosis observed in patients with cancer displaying elevated levels of G9a/H3K9me3.",
author = "Vincent Gaggioli and Lo, {Calvin S.Y.} and Nazaret Rever{\'o}n-G{\'o}mez and Zuzana Jasencakova and Heura Domenech and Hong Nguyen and Simone Sidoli and Andrey Tvardovskiy and Sidrit Uruci and Slotman, {Johan A.} and Yi Chai and Gon{\c c}alves, {Jo{\~a}o G.S.C.Souto} and Manolika, {Eleni Maria} and Jensen, {Ole N.} and David Wheeler and Sriram Sridharan and Sanjiban Chakrabarty and Jeroen Demmers and Roland Kanaar and Anja Groth and Nitika Taneja",
note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
doi = "10.1038/s41556-023-01167-z",
language = "English",
volume = "25",
pages = "1017--1032",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "nature publishing group",
number = "7",

}

RIS

TY - JOUR

T1 - Dynamic de novo heterochromatin assembly and disassembly at replication forks ensures fork stability

AU - Gaggioli, Vincent

AU - Lo, Calvin S.Y.

AU - Reverón-Gómez, Nazaret

AU - Jasencakova, Zuzana

AU - Domenech, Heura

AU - Nguyen, Hong

AU - Sidoli, Simone

AU - Tvardovskiy, Andrey

AU - Uruci, Sidrit

AU - Slotman, Johan A.

AU - Chai, Yi

AU - Gonçalves, João G.S.C.Souto

AU - Manolika, Eleni Maria

AU - Jensen, Ole N.

AU - Wheeler, David

AU - Sridharan, Sriram

AU - Chakrabarty, Sanjiban

AU - Demmers, Jeroen

AU - Kanaar, Roland

AU - Groth, Anja

AU - Taneja, Nitika

N1 - Publisher Copyright: © 2023, The Author(s).

PY - 2023

Y1 - 2023

N2 - Chromatin is dynamically reorganized when DNA replication forks are challenged. However, the process of epigenetic reorganization and its implication for fork stability is poorly understood. Here we discover a checkpoint-regulated cascade of chromatin signalling that activates the histone methyltransferase EHMT2/G9a to catalyse heterochromatin assembly at stressed replication forks. Using biochemical and single molecule chromatin fibre approaches, we show that G9a together with SUV39h1 induces chromatin compaction by accumulating the repressive modifications, H3K9me1/me2/me3, in the vicinity of stressed replication forks. This closed conformation is also favoured by the G9a-dependent exclusion of the H3K9-demethylase JMJD1A/KDM3A, which facilitates heterochromatin disassembly upon fork restart. Untimely heterochromatin disassembly from stressed forks by KDM3A enables PRIMPOL access, triggering single-stranded DNA gap formation and sensitizing cells towards chemotherapeutic drugs. These findings may help in explaining chemotherapy resistance and poor prognosis observed in patients with cancer displaying elevated levels of G9a/H3K9me3.

AB - Chromatin is dynamically reorganized when DNA replication forks are challenged. However, the process of epigenetic reorganization and its implication for fork stability is poorly understood. Here we discover a checkpoint-regulated cascade of chromatin signalling that activates the histone methyltransferase EHMT2/G9a to catalyse heterochromatin assembly at stressed replication forks. Using biochemical and single molecule chromatin fibre approaches, we show that G9a together with SUV39h1 induces chromatin compaction by accumulating the repressive modifications, H3K9me1/me2/me3, in the vicinity of stressed replication forks. This closed conformation is also favoured by the G9a-dependent exclusion of the H3K9-demethylase JMJD1A/KDM3A, which facilitates heterochromatin disassembly upon fork restart. Untimely heterochromatin disassembly from stressed forks by KDM3A enables PRIMPOL access, triggering single-stranded DNA gap formation and sensitizing cells towards chemotherapeutic drugs. These findings may help in explaining chemotherapy resistance and poor prognosis observed in patients with cancer displaying elevated levels of G9a/H3K9me3.

U2 - 10.1038/s41556-023-01167-z

DO - 10.1038/s41556-023-01167-z

M3 - Journal article

C2 - 37414849

AN - SCOPUS:85164110736

VL - 25

SP - 1017

EP - 1032

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 7

ER -

ID: 360403826