Transposition with Tn3-family elements occurs through interaction with the host β-sliding clamp processivity factor

Author:

Tang Yu1,Zhang Jianfeng23ORCID,Guan Jiahao3,Liang Wei4ORCID,Petassi Michael T5,Zhang Yumeng3ORCID,Jiang Xiaofei6,Wang Minggui2ORCID,Wu Wenjuan1,Ou Hong-Yu3ORCID,Peters Joseph E5ORCID

Affiliation:

1. Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine , Shanghai 200123 , China

2. Institute of Antibiotics, Huashan Hospital, Fudan University , Shanghai 200040 , China

3. State Key Laboratory of Microbial Metabolism, Joint International Laboratory on Metabolic & Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University , Shanghai 200240 , China

4. Department of Laboratory Medicine, The First Affiliated Hospital of Ningbo University , Ningbo 315010 , China

5. Department of Microbiology, Cornell University , Ithaca , NY 14853 , USA

6. Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University , Shanghai 200040 , China

Abstract

Abstract Tn3 family transposons are a widespread group of replicative transposons, notorious for contributing to the dissemination of antibiotic resistance, particularly the global prevalence of carbapenem resistance. The transposase (TnpA) of these elements catalyzes DNA breakage and rejoining reactions required for transposition. However, the molecular mechanism for target site selection with these elements remains unclear. Here, we identify a QLxxLR motif in N-terminal of Tn3 TnpAs and demonstrate that this motif allows interaction between TnpA of Tn3 family transposon Tn1721 and the host β-sliding clamp (DnaN), the major processivity factor of the DNA replication machinery. The TnpA-DnaN interaction is essential for Tn1721 transposition. Our work unveils a mechanism whereby Tn3 family transposons can bias transposition into certain replisomes through an interaction with the host replication machinery. This study further expands the diversity of mobile elements that use interaction with the host replication machinery to bias integration.

Funder

National Natural Science Foundation of China

Shanghai Sailing Program

National Institutes of Health

Publisher

Oxford University Press (OUP)

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