Loss of DHX15 Function Impairs Hematopoiesis in Vav-Dhx15-KO Mice and Cause DNA Damage-Induced Cell Cycle Arrest and Apoptosis in Leukemia Cell Lines

Wang, Xuechun; Ye, Luya; Cai, Yuanhua; Li, Qiao; Chen, Zhixiang; Tu, Fuquan; Lai, Xiaolin; Pan, Lili; Li, Yang; Li, Xiaofan; Wang, Shaoyuan

doi:10.1182/blood-2022-164557

Blood

2022

DOI: 10.1182/blood-2022-164557

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Loss of DHX15 Function Impairs Hematopoiesis in Vav-Dhx15-KO Mice and Cause DNA Damage-Induced Cell Cycle Arrest and Apoptosis in Leukemia Cell Lines

Xuechun Wang

Luya Ye

Yuanhua Cai

et al.

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2024

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DHX15 inhibits mouse APOBEC3 deamination

Zhao,

Ross

2024

Preprint

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APOBEC3 family proteins are critical host factors that counteract and prevent the replication of retroviruses and other viruses through cytidine deamination. Human APOBEC3G inactivates HIV-1 through the introduction of lethal mutations to viral genomes. In contrast, mouse APOBEC3 does not induce DNA hypermutation of murine retroviruses, although it retains functional cytidine deaminase activity. Why mouse APOBEC3 does not effectively deaminate murine retroviruses is still unknown. In this study, we found that the dead box helicase DHX15 interacts with mouse APOBEC3 and inhibits its deamination activity. DHX15 was packaged into murine leukemia virus (MLV) virions independent of its binding with APOBEC3. Moreover, DHX15 knockdown inhibited MLV replication and resulted in more G-to-A mutations in proviral DNA. Finally, DHX15 knockdown induced DNA damage in murine cells, suggesting that it plays a role in preserving genome integrity in cells expressing mouse APOBEC3 protein.

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DHX15 inhibits mouse APOBEC3 deamination

Zhao,

Ross

2024

Preprint

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Loss of DHX15 Function Impairs Hematopoiesis in Vav-Dhx15-KO Mice and Cause DNA Damage-Induced Cell Cycle Arrest and Apoptosis in Leukemia Cell Lines

Cited by 1 publication

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DHX15 inhibits mouse APOBEC3 deamination

DHX15 inhibits mouse APOBEC3 deamination

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