RAD51 protects human cells from transcription-replication conflicts

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

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RAD51 protects human cells from transcription-replication conflicts. / Bhowmick, Rahul; Lerdrup, Mads; Gadi, Sampath Amitash; Rossetti, Giacomo G.; Singh, Manika I.; Liu, Ying; Halazonetis, Thanos D.; Hickson, Ian D.

In: Molecular Cell, Vol. 82, No. 18, 2022, p. 3366-3381.e9.

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

Harvard

Bhowmick, R, Lerdrup, M, Gadi, SA, Rossetti, GG, Singh, MI, Liu, Y, Halazonetis, TD & Hickson, ID 2022, 'RAD51 protects human cells from transcription-replication conflicts', Molecular Cell, vol. 82, no. 18, pp. 3366-3381.e9. https://doi.org/10.1016/j.molcel.2022.07.010

APA

Bhowmick, R., Lerdrup, M., Gadi, S. A., Rossetti, G. G., Singh, M. I., Liu, Y., Halazonetis, T. D., & Hickson, I. D. (2022). RAD51 protects human cells from transcription-replication conflicts. Molecular Cell, 82(18), 3366-3381.e9. https://doi.org/10.1016/j.molcel.2022.07.010

Vancouver

Bhowmick R, Lerdrup M, Gadi SA, Rossetti GG, Singh MI, Liu Y et al. RAD51 protects human cells from transcription-replication conflicts. Molecular Cell. 2022;82(18):3366-3381.e9. https://doi.org/10.1016/j.molcel.2022.07.010

Author

Bhowmick, Rahul ; Lerdrup, Mads ; Gadi, Sampath Amitash ; Rossetti, Giacomo G. ; Singh, Manika I. ; Liu, Ying ; Halazonetis, Thanos D. ; Hickson, Ian D. / RAD51 protects human cells from transcription-replication conflicts. In: Molecular Cell. 2022 ; Vol. 82, No. 18. pp. 3366-3381.e9.

Bibtex

@article{2a25c17861ce4f9fb132fa3acc78c8b8,
title = "RAD51 protects human cells from transcription-replication conflicts",
abstract = "Oncogene activation during tumorigenesis promotes DNA replication stress (RS), which subsequently drives the formation of cancer-associated chromosomal rearrangements. Many episodes of physiological RS likely arise due to conflicts between the DNA replication and transcription machineries operating simultaneously at the same loci. One role of the RAD51 recombinase in human cells is to protect replication forks undergoing RS. Here, we have identified a key role for RAD51 in preventing transcription-replication conflicts (TRCs) from triggering replication fork breakage. The genomic regions most affected by RAD51 deficiency are characterized by being replicated and transcribed in early S-phase and show significant overlap with loci prone to cancer-associated amplification. Consistent with a role for RAD51 in protecting against transcription-replication conflicts, many of the adverse effects of RAD51 depletion are ameliorated by inhibiting early S-phase transcription. We propose a model whereby RAD51 suppresses fork breakage and subsequent inadvertent amplification of genomic loci prone to experiencing TRCs.",
keywords = "common fragile sites, gene amplification in cancer, mitotic DNA synthesis, oncogene-induced DNA replication stress, replication fork protection",
author = "Rahul Bhowmick and Mads Lerdrup and Gadi, {Sampath Amitash} and Rossetti, {Giacomo G.} and Singh, {Manika I.} and Ying Liu and Halazonetis, {Thanos D.} and Hickson, {Ian D.}",
note = "Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
doi = "10.1016/j.molcel.2022.07.010",
language = "English",
volume = "82",
pages = "3366--3381.e9",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "18",

}

RIS

TY - JOUR

T1 - RAD51 protects human cells from transcription-replication conflicts

AU - Bhowmick, Rahul

AU - Lerdrup, Mads

AU - Gadi, Sampath Amitash

AU - Rossetti, Giacomo G.

AU - Singh, Manika I.

AU - Liu, Ying

AU - Halazonetis, Thanos D.

AU - Hickson, Ian D.

N1 - Publisher Copyright: © 2022 Elsevier Inc.

PY - 2022

Y1 - 2022

N2 - Oncogene activation during tumorigenesis promotes DNA replication stress (RS), which subsequently drives the formation of cancer-associated chromosomal rearrangements. Many episodes of physiological RS likely arise due to conflicts between the DNA replication and transcription machineries operating simultaneously at the same loci. One role of the RAD51 recombinase in human cells is to protect replication forks undergoing RS. Here, we have identified a key role for RAD51 in preventing transcription-replication conflicts (TRCs) from triggering replication fork breakage. The genomic regions most affected by RAD51 deficiency are characterized by being replicated and transcribed in early S-phase and show significant overlap with loci prone to cancer-associated amplification. Consistent with a role for RAD51 in protecting against transcription-replication conflicts, many of the adverse effects of RAD51 depletion are ameliorated by inhibiting early S-phase transcription. We propose a model whereby RAD51 suppresses fork breakage and subsequent inadvertent amplification of genomic loci prone to experiencing TRCs.

AB - Oncogene activation during tumorigenesis promotes DNA replication stress (RS), which subsequently drives the formation of cancer-associated chromosomal rearrangements. Many episodes of physiological RS likely arise due to conflicts between the DNA replication and transcription machineries operating simultaneously at the same loci. One role of the RAD51 recombinase in human cells is to protect replication forks undergoing RS. Here, we have identified a key role for RAD51 in preventing transcription-replication conflicts (TRCs) from triggering replication fork breakage. The genomic regions most affected by RAD51 deficiency are characterized by being replicated and transcribed in early S-phase and show significant overlap with loci prone to cancer-associated amplification. Consistent with a role for RAD51 in protecting against transcription-replication conflicts, many of the adverse effects of RAD51 depletion are ameliorated by inhibiting early S-phase transcription. We propose a model whereby RAD51 suppresses fork breakage and subsequent inadvertent amplification of genomic loci prone to experiencing TRCs.

KW - common fragile sites

KW - gene amplification in cancer

KW - mitotic DNA synthesis

KW - oncogene-induced DNA replication stress

KW - replication fork protection

U2 - 10.1016/j.molcel.2022.07.010

DO - 10.1016/j.molcel.2022.07.010

M3 - Journal article

C2 - 36002000

AN - SCOPUS:85137836331

VL - 82

SP - 3366-3381.e9

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 18

ER -

ID: 320495903