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image of In-silico Comparative Analysis of TOP3B Protein Mammals Species with Emphasis on Heterocephalus glaber and Homo sapiens

Abstract

Introduction

TOP3B (Topoisomerase III-Beta) is a DNA topoisomerase enzyme essential for managing DNA topology during various cellular processes. TOP3B knockout mice typically develop but have a shorter lifespan; however, the exact role of TOP3B is not fully understood. This study aims to investigate the diversity of TOP3B across various mammalian species, with a particular focus on comparing the naked mole-rat (), known for its exceptional longevity and genomic stability, and humans ().

Methods

The study analyzed 30 putative TOP3B genes across 23 mammalian species, including and ). Further deep analysis was done by covering structural and functional delivery analysis.

Results

Database searches revealed the presence of two transcript isoforms, X1 and X3, in the naked mole-rat (NMR) and three isoforms in humans (), while most other species exhibited one to two isoforms. Analyses of conserved domain architecture and de novo motifs indicated noticeable differences in the domain and motif patterns between the NMR and human isoforms. Additionally, multiple sequence alignment identified several mutations at critical sites in the NMR's TOP3B protein, including A46D and G47S, and five other unnamed mutations that may contribute to genomic stability. Evolutionary analyses showed that the TOP3B sequences of the NMR are closely related to those of (guinea pig) and (Degus). Furthermore, protein-protein interaction network analyses, along with pathway and molecular docking studies, revealed significant diversity in the interaction patterns of TOP3B between the NMR and humans.

Discussion

The structural diversity and conserved-site mutations in ’s TOP3B protein suggest a potential role in promoting genomic stability and extending lifespan. These unique structural features may contribute to the exceptional resistance to genomic instability and aging, offering insights into potential longevity mechanisms.

Conclusion

These findings suggest that structure variations and mutations in NMR’s TOP3B protein are associated with enhanced genomic stability, which may underlie its remarkable lifespan. This study provides preliminary insights into the potential function of TOP3B in genomic maintenance across species, particularly in aging and longevity.

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2025-03-10
2025-09-14
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  • Article Type:
    Research Article
Keywords: TOP3B ; naked mole-rat ; genomic stability ; conserved domains ; human ; protein docking
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