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 journal › Journal article › Research › peer-review
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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
C2 - 29021206
AN - SCOPUS:85032676114
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