A distinct role for recombination repair factors in an early cellular response to transcription-replication conflicts

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

Standard

A distinct role for recombination repair factors in an early cellular response to transcription-replication conflicts. / Shao, Xin; Joergensen, Amalie M.; Howlett, Niall G.; Lisby, Michael; Oestergaard, Vibe H.

In: Nucleic Acids Research, Vol. 48, No. 10, 2020, p. 5467-5484.

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

Harvard

Shao, X, Joergensen, AM, Howlett, NG, Lisby, M & Oestergaard, VH 2020, 'A distinct role for recombination repair factors in an early cellular response to transcription-replication conflicts', Nucleic Acids Research, vol. 48, no. 10, pp. 5467-5484. https://doi.org/10.1093/nar/gkaa268

APA

Shao, X., Joergensen, A. M., Howlett, N. G., Lisby, M., & Oestergaard, V. H. (2020). A distinct role for recombination repair factors in an early cellular response to transcription-replication conflicts. Nucleic Acids Research, 48(10), 5467-5484. https://doi.org/10.1093/nar/gkaa268

Vancouver

Shao X, Joergensen AM, Howlett NG, Lisby M, Oestergaard VH. A distinct role for recombination repair factors in an early cellular response to transcription-replication conflicts. Nucleic Acids Research. 2020;48(10):5467-5484. https://doi.org/10.1093/nar/gkaa268

Author

Shao, Xin ; Joergensen, Amalie M. ; Howlett, Niall G. ; Lisby, Michael ; Oestergaard, Vibe H. / A distinct role for recombination repair factors in an early cellular response to transcription-replication conflicts. In: Nucleic Acids Research. 2020 ; Vol. 48, No. 10. pp. 5467-5484.

Bibtex

@article{cfd0fcb29bf24689bdec7f722cac72b4,
title = "A distinct role for recombination repair factors in an early cellular response to transcription-replication conflicts",
abstract = "Transcription-replication (T-R) conflicts are profound threats to genome integrity. However, whilst much is known about the existence of T-R conflicts, our understanding of the genetic and temporal nature of how cells respond to them is poorly established. Here, we address this by characterizing the early cellular response to transient T-R conflicts (TRe). This response specifically requires the DNA recombination repair proteins BLM and BRCA2 as well as a non-canonical monoubiquitylation-independent function of FANCD2. A hallmark of the TRe response is the rapid co-localization of these three DNA repair factors at sites of T-R collisions. We find that the TRe response relies on basal activity of the ATR kinase, yet it does not lead to hyperactivation of this key checkpoint protein. Furthermore, specific abrogation of the TRe response leads to DNA damage in mitosis, and promotes chromosome instability and cell death. Collectively our findings identify a new role for these well-established tumor suppressor proteins at an early stage of the cellular response to conflicts between DNA transcription and replication.",
author = "Xin Shao and Joergensen, {Amalie M.} and Howlett, {Niall G.} and Michael Lisby and Oestergaard, {Vibe H.}",
year = "2020",
doi = "10.1093/nar/gkaa268",
language = "English",
volume = "48",
pages = "5467--5484",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "10",

}

RIS

TY - JOUR

T1 - A distinct role for recombination repair factors in an early cellular response to transcription-replication conflicts

AU - Shao, Xin

AU - Joergensen, Amalie M.

AU - Howlett, Niall G.

AU - Lisby, Michael

AU - Oestergaard, Vibe H.

PY - 2020

Y1 - 2020

N2 - Transcription-replication (T-R) conflicts are profound threats to genome integrity. However, whilst much is known about the existence of T-R conflicts, our understanding of the genetic and temporal nature of how cells respond to them is poorly established. Here, we address this by characterizing the early cellular response to transient T-R conflicts (TRe). This response specifically requires the DNA recombination repair proteins BLM and BRCA2 as well as a non-canonical monoubiquitylation-independent function of FANCD2. A hallmark of the TRe response is the rapid co-localization of these three DNA repair factors at sites of T-R collisions. We find that the TRe response relies on basal activity of the ATR kinase, yet it does not lead to hyperactivation of this key checkpoint protein. Furthermore, specific abrogation of the TRe response leads to DNA damage in mitosis, and promotes chromosome instability and cell death. Collectively our findings identify a new role for these well-established tumor suppressor proteins at an early stage of the cellular response to conflicts between DNA transcription and replication.

AB - Transcription-replication (T-R) conflicts are profound threats to genome integrity. However, whilst much is known about the existence of T-R conflicts, our understanding of the genetic and temporal nature of how cells respond to them is poorly established. Here, we address this by characterizing the early cellular response to transient T-R conflicts (TRe). This response specifically requires the DNA recombination repair proteins BLM and BRCA2 as well as a non-canonical monoubiquitylation-independent function of FANCD2. A hallmark of the TRe response is the rapid co-localization of these three DNA repair factors at sites of T-R collisions. We find that the TRe response relies on basal activity of the ATR kinase, yet it does not lead to hyperactivation of this key checkpoint protein. Furthermore, specific abrogation of the TRe response leads to DNA damage in mitosis, and promotes chromosome instability and cell death. Collectively our findings identify a new role for these well-established tumor suppressor proteins at an early stage of the cellular response to conflicts between DNA transcription and replication.

U2 - 10.1093/nar/gkaa268

DO - 10.1093/nar/gkaa268

M3 - Journal article

C2 - 32329774

AN - SCOPUS:85085904434

VL - 48

SP - 5467

EP - 5484

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 10

ER -

ID: 243150408