hSSB2 (NABP1) is required for the recruitment of RPA during the cellular response to DNA UV damage

Maintenance of genomic stability is critical to prevent diseases such as cancer. As such, eukaryotic cells have multiple pathways to efficiently detect, signal and repair DNA damage. One common form of exogenous DNA damage comes from ultraviolet B (UVB) radiation. UVB generates cyclobutane pyrimidine dimers (CPD) that must be rapidly detected and repaired to maintain the genetic code. The nucleotide excision repair (NER) pathway is the main repair system for this type of DNA damage. Here, we determined the role of the human Single-Stranded DNA Binding protein 2, hSSB2, in the response to UVB exposure. We demonstrate that hSSB2 levels increase in vitro and in vivo after UVB irradiation and that hSSB2 rapidly binds to chromatin. Depletion of hSSB2 results in significantly decreased Replication Protein A (RPA32) phosphorylation and impaired RPA32 localisation to the site of UV-induced DNA damage. Delayed recruitment of NER protein Xeroderma Pigmentosum group C (XPC) was also observed, leading to increased cellular sensitivity to UVB. Finally, hSSB2 was shown to have affinity for single-strand DNA containing a single CPD and for duplex DNA with a two-base mismatch mimicking a CPD moiety. Altogether our data demonstrate that hSSB2 is involved in the cellular response to UV exposure.

Automated summary

This study identified the critical role of human Single-Stranded DNA Binding protein 2 (hSSB2) in cellular response to UV exposure, including its rapid chromatin binding, impact on Replication Protein A (RPA32) phosphorylation, delayed recruitment of Xeroderma Pigmentosum group C (XPC), and increased cellular sensitivity to UVB. Moreover, hSSB2 was found to have affinity for single-strand DNA with CPD and duplex DNA mimicking a CPD moiety, demonstrating its involvement in DNA damage repair mechanisms in response to UV exposure.