• PMID: 30528234
• Gene Name: TOPBP1
• Condition: Spermatogenetic defects
• Association: Associated
• Sex: Male
• Infertility type: Male infertility

TopBP1 deficiency impairs the localization of proteins involved in early recombination and results in meiotic chromosome defects during spermatogenesis

Jeon Y, Park MK, Kim SM, Bae JS, Lee CW, Lee H.

Topoisomerase IIβ-binding protein 1 (TopBP1) is BRCT domain-containing protein that is required for DNA double-strand break (DSB) repair and DNA damage responses; however, its function during the early stage of spermatogenesis is still unclear. To investigate the physiological role of TopBP1, we have generated germ cell-specific TopBP1-depleted mouse model. TopBP1-deleted mice were infertile, showed a loss of germ cells and had meiotic defects. Conditional TopBP1 deletion resulted in reduced testis size, reduced number of epididymal sperm, increased apoptosis, and severely compromised fertility. TopBP1 deficiency caused defects in DMC1 and Rad51 foci formation, abnormal synaptonemal complexes and meiotic chromosome defects. Collectively, these results suggest that TopBP1 deficiency during spermatogenesis impairs the localization of proteins involved in early recombination at DSBs, results in meiotic chromosome defects and leads to infertility. CI - Copyright © 2018 Elsevier Inc. All rights reserved. FAU - Jeon, Yoon AU - Jeon Y AD - Carcinogenesis and Metastasis Research Branch, National Cancer Center, Gyeonggi, Republic of Korea; Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea. FAU - Park, Mi Kyung AU - Park MK AD - Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Gyeonggi, Republic of Korea. FAU - Kim, Sun Mi AU - Kim SM AD - Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Gyeonggi, Republic of Korea. FAU - Bae, June Sung AU - Bae JS AD - Carcinogenesis and Metastasis Research Branch, National Cancer Center, Gyeonggi, Republic of Korea. FAU - Lee, Chang Woo AU - Lee CW AD - Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.