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

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Documents

Lisa Schubert, Teresa Ho, Saskia Hoffmann, Peter Haahr, Claire Guérillon, Niels Mailand

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.

Original languageEnglish
JournalEMBO Reports
Volume18
Issue number11
Pages (from-to)1991-2003
Number of pages13
ISSN1469-221X
DOIs
Publication statusPublished - Nov 2017

    Research areas

  • DNA replication, genome integrity, replication protein A, replication stress, single-stranded DNA

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