The CMG Helicase Bypasses DNA-Protein Cross-Links to Facilitate Their Repair

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The CMG Helicase Bypasses DNA-Protein Cross-Links to Facilitate Their Repair. / Sparks, Justin L; Chistol, Gheorghe; Gao, Alan O.; Räschle, Markus; Larsen, Nicolai B.; Mann, Matthias; Duxin, Julien P.; Walter, Johannes C.

In: Cell, Vol. 176, No. 1-2, 2019, p. 167-181.e21.

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

Harvard

Sparks, JL, Chistol, G, Gao, AO, Räschle, M, Larsen, NB, Mann, M, Duxin, JP & Walter, JC 2019, 'The CMG Helicase Bypasses DNA-Protein Cross-Links to Facilitate Their Repair', Cell, vol. 176, no. 1-2, pp. 167-181.e21. https://doi.org/10.1016/j.cell.2018.10.053

APA

Sparks, J. L., Chistol, G., Gao, A. O., Räschle, M., Larsen, N. B., Mann, M., Duxin, J. P., & Walter, J. C. (2019). The CMG Helicase Bypasses DNA-Protein Cross-Links to Facilitate Their Repair. Cell, 176(1-2), 167-181.e21. https://doi.org/10.1016/j.cell.2018.10.053

Vancouver

Sparks JL, Chistol G, Gao AO, Räschle M, Larsen NB, Mann M et al. The CMG Helicase Bypasses DNA-Protein Cross-Links to Facilitate Their Repair. Cell. 2019;176(1-2):167-181.e21. https://doi.org/10.1016/j.cell.2018.10.053

Author

Sparks, Justin L ; Chistol, Gheorghe ; Gao, Alan O. ; Räschle, Markus ; Larsen, Nicolai B. ; Mann, Matthias ; Duxin, Julien P. ; Walter, Johannes C. / The CMG Helicase Bypasses DNA-Protein Cross-Links to Facilitate Their Repair. In: Cell. 2019 ; Vol. 176, No. 1-2. pp. 167-181.e21.

Bibtex

@article{12518d20b7054b47afa5d26d713f7bb9,
title = "The CMG Helicase Bypasses DNA-Protein Cross-Links to Facilitate Their Repair",
abstract = "Covalent DNA-protein cross-links (DPCs) impede replication fork progression and threaten genome integrity. Using Xenopus egg extracts, we previously showed that replication fork collision with DPCs causes their proteolysis, followed by translesion DNA synthesis. We show here that when DPC proteolysis is blocked, the replicative DNA helicase CMG (CDC45, MCM2-7, GINS), which travels on the leading strand template, bypasses an intact leading strand DPC. Single-molecule imaging reveals that GINS does not dissociate from CMG during bypass and that CMG slows dramatically after bypass, likely due to uncoupling from the stalled leading strand. The DNA helicase RTEL1 facilitates bypass, apparently by generating single-stranded DNA beyond the DPC. The absence of RTEL1 impairs DPC proteolysis, suggesting that CMG must bypass the DPC to enable proteolysis. Our results suggest a mechanism that prevents inadvertent CMG destruction by DPC proteases, and they reveal CMG's remarkable capacity to overcome obstacles on its translocation strand.",
author = "Sparks, {Justin L} and Gheorghe Chistol and Gao, {Alan O.} and Markus R{\"a}schle and Larsen, {Nicolai B.} and Matthias Mann and Duxin, {Julien P.} and Walter, {Johannes C.}",
year = "2019",
doi = "10.1016/j.cell.2018.10.053",
language = "English",
volume = "176",
pages = "167--181.e21",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "1-2",

}

RIS

TY - JOUR

T1 - The CMG Helicase Bypasses DNA-Protein Cross-Links to Facilitate Their Repair

AU - Sparks, Justin L

AU - Chistol, Gheorghe

AU - Gao, Alan O.

AU - Räschle, Markus

AU - Larsen, Nicolai B.

AU - Mann, Matthias

AU - Duxin, Julien P.

AU - Walter, Johannes C.

PY - 2019

Y1 - 2019

N2 - Covalent DNA-protein cross-links (DPCs) impede replication fork progression and threaten genome integrity. Using Xenopus egg extracts, we previously showed that replication fork collision with DPCs causes their proteolysis, followed by translesion DNA synthesis. We show here that when DPC proteolysis is blocked, the replicative DNA helicase CMG (CDC45, MCM2-7, GINS), which travels on the leading strand template, bypasses an intact leading strand DPC. Single-molecule imaging reveals that GINS does not dissociate from CMG during bypass and that CMG slows dramatically after bypass, likely due to uncoupling from the stalled leading strand. The DNA helicase RTEL1 facilitates bypass, apparently by generating single-stranded DNA beyond the DPC. The absence of RTEL1 impairs DPC proteolysis, suggesting that CMG must bypass the DPC to enable proteolysis. Our results suggest a mechanism that prevents inadvertent CMG destruction by DPC proteases, and they reveal CMG's remarkable capacity to overcome obstacles on its translocation strand.

AB - Covalent DNA-protein cross-links (DPCs) impede replication fork progression and threaten genome integrity. Using Xenopus egg extracts, we previously showed that replication fork collision with DPCs causes their proteolysis, followed by translesion DNA synthesis. We show here that when DPC proteolysis is blocked, the replicative DNA helicase CMG (CDC45, MCM2-7, GINS), which travels on the leading strand template, bypasses an intact leading strand DPC. Single-molecule imaging reveals that GINS does not dissociate from CMG during bypass and that CMG slows dramatically after bypass, likely due to uncoupling from the stalled leading strand. The DNA helicase RTEL1 facilitates bypass, apparently by generating single-stranded DNA beyond the DPC. The absence of RTEL1 impairs DPC proteolysis, suggesting that CMG must bypass the DPC to enable proteolysis. Our results suggest a mechanism that prevents inadvertent CMG destruction by DPC proteases, and they reveal CMG's remarkable capacity to overcome obstacles on its translocation strand.

U2 - 10.1016/j.cell.2018.10.053

DO - 10.1016/j.cell.2018.10.053

M3 - Journal article

C2 - 30595447

VL - 176

SP - 167-181.e21

JO - Cell

JF - Cell

SN - 0092-8674

IS - 1-2

ER -

ID: 211995460