A structural analysis of DNA binding by hSSB1 (NABP2/OBFC2B) in solution

Touma, Christine, Kariawasam, Ruvini, Gimenez, Adrian X., Bernardo, Ray E., Ashton, Nicholas W., Adams, Mark N., Paquet, Nicolas, Croll, Tristan I., O'Byrne, Kenneth J., Richard, Derek J., Cubeddu, Liza, & Gamsjaeger, Roland (2016) A structural analysis of DNA binding by hSSB1 (NABP2/OBFC2B) in solution. Nucleic Acids Research. (In Press)

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Abstract

Single-stranded DNA binding proteins (SSBs) play an important role in DNA processing events such as replication, recombination and repair. Human single-stranded DNA binding protein 1 (hSSB1/NABP2/OBFC2B) contains a single oligosaccharide/oligonucleotide binding (OB) domain followed by a charged C-terminus and is structurally homologous to the SSB from the hyperthermophilic crenarchaeote Sulfolobus solfataricus. Recent work has revealed that hSSB1 is critical to homologous recombination and numerous other important biological processes such as the regulation of telomeres, the maintenance of DNA replication forks and oxidative damage repair. Since the ability of hSSB1 to directly interact with single-stranded DNA (ssDNA) is paramount for all of these processes, understanding the molecular details of ssDNA recognition is essential. In this study, we have used solution-state nuclear magnetic resonance in combination with biophysical and functional experiments to structurally analyse ssDNA binding by hSSB1. We reveal that ssDNA recognition in solution is modulated by base-stacking of four key aromatic residues within the OB domain. This DNA binding mode differs significantly from the recently determined crystal structure of the SOSS1 complex containing hSSB1 and ssDNA. Our findings elucidate the detailed molecular mechanism in solution of ssDNA binding by hSSB1, a major player in the maintenance of genomic stability.

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ID Code: 98785
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: DNA binding, hSSB1/NABP2/OBFC2B, human single-stranded DNA binding protein 1, structural analysis
DOI: 10.1093/nar/gkw617
ISSN: 1362-4962
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Genetics (111203)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Funding:
Copyright Owner: Copyright 2016 The Author(s); Published by Oxford University Press on behalf of Nucleic Acids Research.
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Deposited On: 13 Sep 2016 01:03
Last Modified: 13 Sep 2016 23:22

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