RADX interacts with single-stranded DNA to promote replication fork stability

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RADX interacts with single-stranded DNA to promote replication fork stability. / Schubert, Lisa; Ho, Teresa; Hoffmann, Saskia; Haahr, Peter; Guérillon, Claire; Mailand, Niels.

In: EMBO Reports, Vol. 18, No. 11, 11.2017, p. 1991-2003.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Schubert, L, Ho, T, Hoffmann, S, Haahr, P, Guérillon, C & Mailand, N 2017, 'RADX interacts with single-stranded DNA to promote replication fork stability', EMBO Reports, vol. 18, no. 11, pp. 1991-2003. https://doi.org/10.15252/embr.201744877

APA

Schubert, L., Ho, T., Hoffmann, S., Haahr, P., Guérillon, C., & Mailand, N. (2017). RADX interacts with single-stranded DNA to promote replication fork stability. EMBO Reports, 18(11), 1991-2003. https://doi.org/10.15252/embr.201744877

Vancouver

Schubert L, Ho T, Hoffmann S, Haahr P, Guérillon C, Mailand N. RADX interacts with single-stranded DNA to promote replication fork stability. EMBO Reports. 2017 Nov;18(11):1991-2003. https://doi.org/10.15252/embr.201744877

Author

Schubert, Lisa ; Ho, Teresa ; Hoffmann, Saskia ; Haahr, Peter ; Guérillon, Claire ; Mailand, Niels. / RADX interacts with single-stranded DNA to promote replication fork stability. In: EMBO Reports. 2017 ; Vol. 18, No. 11. pp. 1991-2003.

Bibtex

@article{41f0ca3419ab4bbc8e094ecd263432a8,
title = "RADX interacts with single-stranded DNA to promote replication fork stability",
abstract = "Single-stranded DNA (ssDNA) regions form as an intermediate in many DNA-associated transactions. Multiple cellular proteins interact with ssDNA via the oligonucleotide/oligosaccharide-binding (OB) fold domain. The heterotrimeric, multi-OB fold domain-containing Replication Protein A (RPA) complex has an essential genome maintenance role, protecting ssDNA regions from nucleolytic degradation and providing a recruitment platform for proteins involved in responses to replication stress and DNA damage. Here, we identify the uncharacterized protein RADX (CXorf57) as an ssDNA-binding factor in human cells. RADX binds ssDNA via an N-terminal OB fold cluster, which mediates its recruitment to sites of replication stress. Deregulation of RADX expression and ssDNA binding leads to enhanced replication fork stalling and degradation, and we provide evidence that a balanced interplay between RADX and RPA ssDNA-binding activities is critical for avoiding these defects. Our findings establish RADX as an important component of cellular pathways that promote DNA replication integrity under basal and stressful conditions by means of multiple ssDNA-binding proteins.",
keywords = "DNA replication, genome integrity, replication protein A, replication stress, single-stranded DNA",
author = "Lisa Schubert and Teresa Ho and Saskia Hoffmann and Peter Haahr and Claire Gu{\'e}rillon and Niels Mailand",
year = "2017",
month = "11",
doi = "10.15252/embr.201744877",
language = "English",
volume = "18",
pages = "1991--2003",
journal = "E M B O Reports",
issn = "1469-221X",
publisher = "Wiley-Blackwell",
number = "11",

}

RIS

TY - JOUR

T1 - RADX interacts with single-stranded DNA to promote replication fork stability

AU - Schubert, Lisa

AU - Ho, Teresa

AU - Hoffmann, Saskia

AU - Haahr, Peter

AU - Guérillon, Claire

AU - Mailand, Niels

PY - 2017/11

Y1 - 2017/11

N2 - Single-stranded DNA (ssDNA) regions form as an intermediate in many DNA-associated transactions. Multiple cellular proteins interact with ssDNA via the oligonucleotide/oligosaccharide-binding (OB) fold domain. The heterotrimeric, multi-OB fold domain-containing Replication Protein A (RPA) complex has an essential genome maintenance role, protecting ssDNA regions from nucleolytic degradation and providing a recruitment platform for proteins involved in responses to replication stress and DNA damage. Here, we identify the uncharacterized protein RADX (CXorf57) as an ssDNA-binding factor in human cells. RADX binds ssDNA via an N-terminal OB fold cluster, which mediates its recruitment to sites of replication stress. Deregulation of RADX expression and ssDNA binding leads to enhanced replication fork stalling and degradation, and we provide evidence that a balanced interplay between RADX and RPA ssDNA-binding activities is critical for avoiding these defects. Our findings establish RADX as an important component of cellular pathways that promote DNA replication integrity under basal and stressful conditions by means of multiple ssDNA-binding proteins.

AB - Single-stranded DNA (ssDNA) regions form as an intermediate in many DNA-associated transactions. Multiple cellular proteins interact with ssDNA via the oligonucleotide/oligosaccharide-binding (OB) fold domain. The heterotrimeric, multi-OB fold domain-containing Replication Protein A (RPA) complex has an essential genome maintenance role, protecting ssDNA regions from nucleolytic degradation and providing a recruitment platform for proteins involved in responses to replication stress and DNA damage. Here, we identify the uncharacterized protein RADX (CXorf57) as an ssDNA-binding factor in human cells. RADX binds ssDNA via an N-terminal OB fold cluster, which mediates its recruitment to sites of replication stress. Deregulation of RADX expression and ssDNA binding leads to enhanced replication fork stalling and degradation, and we provide evidence that a balanced interplay between RADX and RPA ssDNA-binding activities is critical for avoiding these defects. Our findings establish RADX as an important component of cellular pathways that promote DNA replication integrity under basal and stressful conditions by means of multiple ssDNA-binding proteins.

KW - DNA replication

KW - genome integrity

KW - replication protein A

KW - replication stress

KW - single-stranded DNA

U2 - 10.15252/embr.201744877

DO - 10.15252/embr.201744877

M3 - Journal article

VL - 18

SP - 1991

EP - 2003

JO - E M B O Reports

JF - E M B O Reports

SN - 1469-221X

IS - 11

ER -

ID: 185995376