53BP1 nuclear bodies enforce replication timing at under-replicated DNA to limit heritable DNA damage

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

Standard

53BP1 nuclear bodies enforce replication timing at under-replicated DNA to limit heritable DNA damage. / Spies, Julian; Lukas, Claudia; Somyajit, Kumar; Rask, Maj-Britt; Lukas, Jiri; Neelsen, Kai John.

In: Nature Cell Biology, Vol. 21, 2019, p. 487-497.

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

Harvard

Spies, J, Lukas, C, Somyajit, K, Rask, M-B, Lukas, J & Neelsen, KJ 2019, '53BP1 nuclear bodies enforce replication timing at under-replicated DNA to limit heritable DNA damage', Nature Cell Biology, vol. 21, pp. 487-497. https://doi.org/10.1038/s41556-019-0293-6

APA

Spies, J., Lukas, C., Somyajit, K., Rask, M-B., Lukas, J., & Neelsen, K. J. (2019). 53BP1 nuclear bodies enforce replication timing at under-replicated DNA to limit heritable DNA damage. Nature Cell Biology, 21, 487-497. https://doi.org/10.1038/s41556-019-0293-6

Vancouver

Spies J, Lukas C, Somyajit K, Rask M-B, Lukas J, Neelsen KJ. 53BP1 nuclear bodies enforce replication timing at under-replicated DNA to limit heritable DNA damage. Nature Cell Biology. 2019;21:487-497. https://doi.org/10.1038/s41556-019-0293-6

Author

Spies, Julian ; Lukas, Claudia ; Somyajit, Kumar ; Rask, Maj-Britt ; Lukas, Jiri ; Neelsen, Kai John. / 53BP1 nuclear bodies enforce replication timing at under-replicated DNA to limit heritable DNA damage. In: Nature Cell Biology. 2019 ; Vol. 21. pp. 487-497.

Bibtex

@article{2c794d01a4294e47818f58af224ed3f8,
title = "53BP1 nuclear bodies enforce replication timing at under-replicated DNA to limit heritable DNA damage",
abstract = "Failure to complete DNA replication is a stochastic by-product of genome doubling in almost every cell cycle. During mitosis, under-replicated DNA (UR-DNA) is converted into DNA lesions, which are inherited by daughter cells and sequestered in 53BP1 nuclear bodies (53BP1-NBs). The fate of such cells remains unknown. Here, we show that the formation of 53BP1-NBs interrupts the chain of iterative damage intrinsically embedded in UR-DNA. Unlike clastogen-induced 53BP1 foci that are repaired throughout interphase, 53BP1-NBs restrain replication of the embedded genomic loci until late S phase, thus enabling the dedicated RAD52-mediated repair of UR-DNA lesions. The absence or malfunction of 53BP1-NBs causes premature replication of the affected loci, accompanied by genotoxic RAD51-mediated recombination. Thus, through adjusting replication timing and repair pathway choice at under-replicated loci, 53BP1-NBs enable the completion of genome duplication of inherited UR-DNA and prevent the conversion of stochastic under-replications into genome instability.",
author = "Julian Spies and Claudia Lukas and Kumar Somyajit and Maj-Britt Rask and Jiri Lukas and Neelsen, {Kai John}",
year = "2019",
doi = "10.1038/s41556-019-0293-6",
language = "English",
volume = "21",
pages = "487--497",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - 53BP1 nuclear bodies enforce replication timing at under-replicated DNA to limit heritable DNA damage

AU - Spies, Julian

AU - Lukas, Claudia

AU - Somyajit, Kumar

AU - Rask, Maj-Britt

AU - Lukas, Jiri

AU - Neelsen, Kai John

PY - 2019

Y1 - 2019

N2 - Failure to complete DNA replication is a stochastic by-product of genome doubling in almost every cell cycle. During mitosis, under-replicated DNA (UR-DNA) is converted into DNA lesions, which are inherited by daughter cells and sequestered in 53BP1 nuclear bodies (53BP1-NBs). The fate of such cells remains unknown. Here, we show that the formation of 53BP1-NBs interrupts the chain of iterative damage intrinsically embedded in UR-DNA. Unlike clastogen-induced 53BP1 foci that are repaired throughout interphase, 53BP1-NBs restrain replication of the embedded genomic loci until late S phase, thus enabling the dedicated RAD52-mediated repair of UR-DNA lesions. The absence or malfunction of 53BP1-NBs causes premature replication of the affected loci, accompanied by genotoxic RAD51-mediated recombination. Thus, through adjusting replication timing and repair pathway choice at under-replicated loci, 53BP1-NBs enable the completion of genome duplication of inherited UR-DNA and prevent the conversion of stochastic under-replications into genome instability.

AB - Failure to complete DNA replication is a stochastic by-product of genome doubling in almost every cell cycle. During mitosis, under-replicated DNA (UR-DNA) is converted into DNA lesions, which are inherited by daughter cells and sequestered in 53BP1 nuclear bodies (53BP1-NBs). The fate of such cells remains unknown. Here, we show that the formation of 53BP1-NBs interrupts the chain of iterative damage intrinsically embedded in UR-DNA. Unlike clastogen-induced 53BP1 foci that are repaired throughout interphase, 53BP1-NBs restrain replication of the embedded genomic loci until late S phase, thus enabling the dedicated RAD52-mediated repair of UR-DNA lesions. The absence or malfunction of 53BP1-NBs causes premature replication of the affected loci, accompanied by genotoxic RAD51-mediated recombination. Thus, through adjusting replication timing and repair pathway choice at under-replicated loci, 53BP1-NBs enable the completion of genome duplication of inherited UR-DNA and prevent the conversion of stochastic under-replications into genome instability.

U2 - 10.1038/s41556-019-0293-6

DO - 10.1038/s41556-019-0293-6

M3 - Journal article

C2 - 30804506

VL - 21

SP - 487

EP - 497

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

ER -

ID: 214126709