Running the gauntlet: challenges to genome integrity in spermiogenesis

ABSTRACT

Species’ continuity depends on gametogenesis to produce the only cell types that can transmit genetic information across generations. Spermiogenesis, which encompasses post-meiotic, haploid stages of male gametogenesis, is a process that leads to the formation of sperm cells well-known for their motility. Spermiogenesis faces three major challenges. First, after two rounds of meiotic divisions, the genome lacks repair templates (no sister chromatids, no homologous chromosomes), making it incredibly vulnerable to any genomic insults over an extended time (typically days-weeks). Second, the sperm genome becomes transcriptionally silent, making it difficult to respond to new perturbations as spermiogenesis progresses. Third, the histone-to-protamine transition, which is essential to package the sperm genome, counterintuitively involves DNA break formation. How spermiogenesis handles these challenges remains poorly understood. In this review, we discuss each challenge and their intersection with the biology of protamines. Finally, we discuss the implication of protamines in the process of evolution.

KEYWORDS:

• DNA damage
• Double stranded breaks (DSB)
• genome integrity
• protamines
• Spermiogenesis

Acknowledgments

We thank the Yamashita lab members for fruitful discussions, and Drs. Jaclyn M. Fingerhut, Amelie A. Raz, and Mark J. Khoury for critical reading of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

MK and YMY conceptualized and wrote the manuscript, and prepared the figures.

Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Additional information

Funding

MK is supported by an HHMI Hanna H. Gray fellowship [GT16770], and research in the Yamashita Lab is supported by the Howard Hughes Medical Institute, John Templeton Foundation [RQ-46367], and Gordon and Betty Moore Foundation [12261] to YMY, as well as the Whitehead Institute for Biomedical Science.