The role of hSSB1 and hSSB2 in the DNA damage response: mechanisms and implications

Vollständiger Abstract

Worum geht es in dieser Arbeit?

Abstract The DNA damage response preserves genome integrity by detecting DNA lesions, activating checkpoint signalling, and coordinating repair with cell-cycle control. Defective or incomplete repair can promote mutation accumulation, chromosomal instability, cancer development, and ageing-associated diseases. In this review, we discuss the human single-stranded DNA-binding proteins hSSB1 and hSSB2, with an emphasis on their roles in ssDNA-rich repair intermediates generated during double-strand break repair, replication stress, oxidative base damage, telomere maintenance, and selected ultraviolet-damage responses. Both proteins contain oligonucleotide/oligosaccharide-binding fold domains that support ssDNA recognition and provide platforms for protein–protein interactions within DNA repair and chromatin-associated pathways. Current evidence identifies hSSB1 as a major regulator of ataxia telangiectasia mutated (ATM)/MRE11–RAD50–NBS1 (MRN)-dependent double-strand break signalling, RAD51-associated homologous recombination, human 8-oxoguanine DNA glycosylase 1 (hOGG1)-mediated repair of 8-oxo-guanine, replication-fork stability, and telomere protection. By contrast, hSSB2 remains less extensively characterised and appears to act in more restricted or context-dependent settings, including the cellular response to ultraviolet-induced DNA damage. We also discuss how post-translational modifications, SOSS/Integrator-associated complexes, transcriptional regulation, and possible epigenetic mechanisms shape hSSB1 and hSSB2 function. Finally, we highlight unresolved questions concerning the extent of functional overlap between these paralogues, the lack of damage-context-specific genome-wide binding maps, and the need to validate whether altered hSSB1 or hSSB2 expression can be exploited as a biomarker or therapeutic vulnerability in cancer.