oligonucleotide/oligosaccharide-binding fold motif is a poly(ADP-ribose)-binding domain that mediates DNA damage response

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 20; pp. 7278 - 7283
• Main Authors: Zhang, Feng, Chen, Yibin, Li, Mo, Yu, Xiaochun
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 20.05.2014; National Acad Sciences
• Subjects: Amino Acid Motifs; Antibodies; Biological Sciences; Cell Line, Tumor; DNA; DNA Damage; DNA Repair; DNA, Single-Stranded - chemistry; DNA-Binding Proteins - chemistry; Eukaryotes; Gene expression regulation; Humans; Lasers; Lesions; Mitochondrial Proteins - chemistry; Nucleic acids; Oligonucleotides - chemistry; Oligosaccharides - chemistry; Photosynthetically active radiation; Poly Adenosine Diphosphate Ribose - chemistry; Prokaryotes; Protein Binding; Protein Folding; Protein Structure, Tertiary; Proteins; Recombinant Proteins - chemistry; Ribonucleic acid; RNA; Small interfering RNA
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1318367111

Oligonucleotide/oligosaccharide-binding (OB) fold is a ssDNA or RNA binding motif in prokaryotes and eukaryotes. Unexpectedly, we found that the OB fold of human ssDNA-binding protein 1 (hSSB1) is a poly(ADP ribose) (PAR) binding domain. hSSB1 exhibits high-affinity binding to PAR and recognizes iso -ADP ribose (ADPR), the linkage between two ADPR units. This interaction between PAR and hSSB1 mediates the early recruitment of hSSB1 to the sites of DNA damage. Mutations in the OB fold of hSSB1 that disrupt PAR binding abolish the relocation of hSSB1 to the sites of DNA damage. Moreover, PAR-mediated recruitment of hSSB1 is important for early DNA damage repair. We have screened other OB folds and found that several other OB folds also recognize PAR. Taken together, our study reveals a PAR-binding domain that mediates DNA damage repair.