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Role of HP1β during spermatogenesis and DNA replication

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Abstract

Heterochromatin protein 1β (HP1β), encoded by the Cbx1 gene, has been functionally linked to chromatin condensation, transcriptional regulation, and DNA damage repair. Here we report that testis-specific Cbx1 conditional knockout (Cbx1 cKO) impairs male germ cell development in mice. Depletion of HP1β negatively affected sperm maturation and increased seminiferous tubule degeneration in Cbx1 cKO mice. In addition, the spermatogonia have elevated γ-H2AX foci levels as do Cbx1 deficient mouse embryonic fibroblasts (MEFs) as compared to wild-type (WT) control MEFs. The increase in γ-H2AX foci in proliferating Cbx1 cKO cells indicates defective replication-dependent DNA damage repair. Depletion or loss of HP1β from human cells and MEFs increased DNA replication fork stalling and firing of new origins of replication, indicating defective DNA synthesis. Taken together, these results suggest that loss of HP1β in proliferating cells leads to DNA replication defects with associated DNA damage that impact spermatogenesis.

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Funding

This study received support from the NIH grants CA129537 and GM109768.

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Authors and Affiliations

  1. Department of Radiation Oncology, The Houston Methodist Research Institute, Houston, TX, 77030, USA

    Vijay Charaka, Anjana Tiwari, Raj K. Pandita, Clayton R. Hunt & Tej K. Pandita

  2. Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA

    Raj K. Pandita & Tej K. Pandita

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  1. Vijay Charaka
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  2. Anjana Tiwari
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  3. Raj K. Pandita
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Contributions

V.C., C.R.H, and T.K.P. directed the study. V.C., C.R.H., and T.K.P. contributed to the design. V.C., A.T., R.K.P., and T.K.P. performed the experiments. V.C., C.H., and T.K.P wrote the paper.

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Correspondence to Tej K. Pandita.

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Charaka, V., Tiwari, A., Pandita, R.K. et al. Role of HP1β during spermatogenesis and DNA replication. Chromosoma 129, 215–226 (2020). https://doi.org/10.1007/s00412-020-00739-4

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  • DOI: https://doi.org/10.1007/s00412-020-00739-4

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