Nabp1-KO Mouse

Nabp1, also known as hSSB2 or OBFC2A, is a single-stranded nucleic-acid-binding protein. It contains an OB (oligonucleotide/oligosaccharide binding) motif at its N-terminus. Nabp1 is involved in the cellular response to DNA UV damage, as it is required for the recruitment of RPA32 and XPC, and it binds to single-stranded DNA containing UV-induced damage like cyclobutane pyrimidine dimers (CPD) [1,5]. It is also part of a high-molecular-mass protein complex in the nucleus and its expression is regulated by RORgamma2 during thymopoiesis [2].

In Ssb2 (Nabp1) knockout mice, the animals are viable and fertile, with no marked phenotypic changes in the thymus, spleen, or testes. Ssb2(-/-) mouse embryonic fibroblasts do not show sensitivity to DNA-damaging agents or defects in DNA repair capacity, suggesting that Ssb1 can compensate for the loss of Ssb2 in mice [4]. In HBV-related HCC, knockdown of NABP1 significantly inhibits the proliferation and migration of HCC cells, and increased NABP1+ malignant hepatocytes are related to poor TACE response and dismal prognosis [3]. Also, in cisplatin-induced acute kidney injury, ZC3H13 promotes the m6A modification of NABP1, enhancing its mRNA stability, and inhibition of ZC3H13 alleviates G2/M cell cycle arrest, apoptosis, and kidney injury by affecting NABP1 expression [6].

In conclusion, Nabp1 plays important roles in DNA damage response and repair, especially in relation to UV-induced DNA damage. The gene knockout mouse models have shown that its loss can be compensated by Ssb1 in some aspects of DNA repair and tissue development. In diseases like HBV-related HCC and cisplatin-induced acute kidney injury, Nabp1 is involved in processes related to cell proliferation, migration, and cell cycle regulation, highlighting its potential as a therapeutic target.

References:

1. Boucher, Didier, Kariawasam, Ruvini, Burgess, Joshua, Khanna, Kum Kum, Richard, Derek J. 2021. hSSB2 (NABP1) is required for the recruitment of RPA during the cellular response to DNA UV damage. In Scientific reports, 11, 20256. doi:10.1038/s41598-021-99355-0. https://pubmed.ncbi.nlm.nih.gov/34642383/

2. Kang, Hong Soon, Beak, Ju Youn, Kim, Yong-Sik, Grissom, Sherry F, Jetten, Anton M. . NABP1, a novel RORgamma-regulated gene encoding a single-stranded nucleic-acid-binding protein. In The Biochemical journal, 397, 89-99. doi:. https://pubmed.ncbi.nlm.nih.gov/16533169/

3. Wang, Libo, Cao, Jiahui, Liu, Zaoqu, Li, Jian, Sun, Yuling. 2024. Enhanced interactions within microenvironment accelerates dismal prognosis in HBV-related HCC after TACE. In Hepatology communications, 8, . doi:10.1097/HC9.0000000000000548. https://pubmed.ncbi.nlm.nih.gov/39365124/

4. Boucher, Didier, Vu, Therese, Bain, Amanda L, Lane, Steven W, Khanna, Kum Kum. 2015. Ssb2/Nabp1 is dispensable for thymic maturation, male fertility, and DNA repair in mice. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 29, 3326-34. doi:10.1096/fj.14-269944. https://pubmed.ncbi.nlm.nih.gov/25917330/

5. Lawson, Teegan, El-Kamand, Serene, Boucher, Didier, Gamsjaeger, Roland, Cubeddu, Liza. 2019. The structural details of the interaction of single-stranded DNA binding protein hSSB2 (NABP1/OBFC2A) with UV-damaged DNA. In Proteins, 88, 319-326. doi:10.1002/prot.25806. https://pubmed.ncbi.nlm.nih.gov/31443132/

6. Sheng, Qinghao, Yu, Qun, Lu, Shangwei, Wang, Rong, Lv, Zhimei. 2025. The inhibition of ZC3H13 attenuates G2/M arrest and apoptosis by alleviating NABP1 m6A modification in cisplatin-induced acute kidney injury. In Cellular and molecular life sciences : CMLS, 82, 86. doi:10.1007/s00018-025-05596-x. https://pubmed.ncbi.nlm.nih.gov/39985591/