Academic journal article Genetics

The Deadbeat Paternal Effect of Uncapped Sperm Telomeres on Cell Cycle Progression and Chromosome Behavior in Drosophila Melanogaster

Academic journal article Genetics

The Deadbeat Paternal Effect of Uncapped Sperm Telomeres on Cell Cycle Progression and Chromosome Behavior in Drosophila Melanogaster

Article excerpt

TELOMERES are the natural ends of linear chromosomes and have distinct properties from broken ends. Multiple proteins are enriched predominantly, if not exclusively, at telomeres and form a capping complex that protects telomeric DNA from engaging in aberrant DNA repair activities. Protein components of the telomere-capping complex (TCC) vary among organisms, in part because species differ in telomeric sequences and whether telomeres are maintained by telomerase or alternative mechanisms (Raffa et al. 2011; Mason et al. 2015). Nonetheless, the TCC's essential functions are well conserved. Failure to assemble TCCs results in telomeric DNA degradation, telomere fusions, and genomic instability.

Mutations in at least 12 loci of Drosophila melanogaster lead to telomere fusions in neuroblasts. Their analysis has led to the identification of telomere-enriched and telomereexclusive proteins required for telomere elongation or TCC assembly, maintenance, or function (Cenci et al. 2005; Pimpinelli 2006). Absence of any one component results in telomere fusions but components have distinct activities (Pimpinelli 2006). For example, heterochromatin protein 1a (HP1a) binds modified histone H3-MeK9 and represses transcription of telomeric retrotransposons and telomere elongation. HP1a also binds DNA and this activity is required for its capping function. The TCC protein HOAP binds DNA and HP1a. Although HOAP is required for capping, it does not affect retrotransposon transcription or telomere elongation. A third protein, HipHop, binds both HP1a and HOAP. HOAP and HipHop are recruited to telomeres by DNA damage checkpoint/repair proteins. Interactions between HP1a, HOAP, and HipHop are required to form stable and functional TCCs (Gao et al. 2010). Similar to yeast and mammalian cells (Stewart et al. 2012), each round of DNA replication in Drosophila somatic cells provides the opportunity to assemble and maintain TCCs. However, a relatively unexplored question is how TCCs, once assembled, are stably maintained in the absence of DNA replication.

The male germ line provides unique opportunities to study telomere dynamics through mitosis, meiosis, and spermiogenesis, which is the postmeiotic period of spermatid differentiation. Telomere maintenance during spermiogenesis is particularly interesting because it is prolonged relative to other spermatogenic stages, lasting ^5.5 days in D. melanogaster (Lindsley and Tokuyasu 1980) and 3.4 weeks in humans (Amann 2008). Moreover, extensive chromatin remodeling occurs. Transformation of round spermatid nuclei to highly condensed sperm heads typically involves histone modification or nearly whole-scale histone replacement by sperm nuclear basic proteins (SNBPs) (Eirin-Lopez and Ausio 2009).

Several studies have been informative for revealing TCC composition in the Drosophila male germ line. In many species, TCCs contain HP1a, HOAP, and HipHop. However, in the melanogaster group species, HipHop has a testis-specific paralog called K81 (Dubruille et al. 2010; Gao et al. 2011). In D. melanogaster, K81 replaces HipHop in early meiosis and k81 mutant males produce sperm lacking TCCs (Dubruille et al. 2010; Gao et al. 2011; Dubruille and Loppin 2015). The consequence is male sterility due to a perplexing paternal effect (Fuyama 1984). Most embryos of k81 fathers arrest by midcleavage but a few survive to late embryogenesis as gynogenetic haploids with only the maternal genome (Fuyama et al. 1988; Yasuda et al. 1995).

Here we describe the Drosophila deadbeat (ddbt) gene and show that Ddbt is an SNBP that acts downstream of K81. Ddbt is recruited to telomeres and ensures that TCCs are maintained through spermiogenesis and transmitted to offspring. We provide evidence that uncapped telomeres delay the onset of the first embryonic anaphase and that the embryo's ability to deal with uncapped telomeres and newly generated breaks changes as it progresses to later cycles. Our findings provide new insights into ddbt's and k81's paternal effect defects and the impact of uncapped telomeres on cell cycle regulation in early embryos. …

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