Abstract 3747: RPS3 positively regulates nucleotide excision repair with respect to XP-D and skin cancers

Abstract

Abstract Ribosomal protein S3 (rpS3) is a multifunctional protein working in translation, DNA repair, cancer, apoptosis etc. UV induced DNA damage is repaired by the nucleotide excision repair (NER) pathways; defects in these pathways lead to a genetic instability known as xeroderma pigmentosum (XP) eventually developing skin cancers. We discovered that rpS3 associates with transcription factor IIH (TFIIH) via an interaction with the xeroderma pigmentosum complementation group D (XPD) protein and complements its function in the NER pathway. Here, we showed that XP-D cells overexpressing rpS3 showed markedly increased resistance to UV through XPD and rpS3 interaction thus augmenting the helicase activity of XPD protein. Additionally, the knockdown of rpS3 caused reduced NER efficiency and the subsequent addition of rpS3 restored the helicase activity of the TFIIH complex in cells. We present data suggesting that rpS3 is involved in post-excision processing in NER, assisting TFIIH in expediting the repair process by increasing its turnover rate when DNA is damaged. We also propose that rpS3 is a novel accessory protein of the NER pathway and its recruitment to the repair machinery upon UV damage augments repair efficiency by enhancing XPD helicase function and increasing its turnover rate, thus facilitating DNA repair. In addition to this, manipulations of rpS3 gene could complement XP-D phenotype and prevent UV damage and skin cancer occurrence. Animal studies strongly indicate that these result could be applied not only for the development of cancer drugs but also for cosmeceuticals. [1] FASEB J. (2020) 34: 8102 [2] Cell & Mol Life Sci (2021) 78: 3591 Citation Format: Joon Kim, Yong-Joon Park, Tae Sung Kim, Woo Sung Ahn, Hag Dong Kim. RPS3 positively regulates nucleotide excision repair with respect to XP-D and skin cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3747.