Human RNA-binding protein HNRNPD interacts with and regulates the repair of deoxyribouridine in DNA

• Published in: International journal of biological macromolecules Vol. 262; no. Pt 1; p. 129951
• Main Authors: Wang, Ziyu, Qu, Minghui, Chang, Sijia, Dai, Xiaoxia, You, Changjun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2024
• Subjects: DNA damage; DNA repair; Proteomics; DNA repair; DNA damage; Proteomics
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.129951

Deoxyribouridine (dU) is an abnormal nucleoside in DNA and plays vital roles in multiple biological and physiological processes. Here, we conducted a mass spectrometry-based screen for dU-binding proteins and found that the heterogeneous nuclear ribonucleoprotein D (HNRNPD) could preferentially bind to dU-containing DNA. We also discovered that HNRNPD engages in the 5-Fluorouracil (5FU)-induced DNA damage response and can modulate the repair of dU in DNA in vitro and in human cells. Moreover, using a shuttle vector- and next-generation sequencing-based method, we unveiled the crucial role of HNRNPD in promoting the replicative bypass of dU in human cells. Taken together, these findings suggested that HNRNPD is a novel dU-bearing DNA-binding protein capable of regulating the removal of dU in DNA, and provided new insights into the molecular mechanisms of dU-associated diseases. [Display omitted]