Abstract
The near complete replacement of somatic chromatin in spermatids is, perhaps, the most striking nuclear event known to the eukaryotic domain. The process is far from being fully understood, but research has nevertheless unraveled its complexity as an expression of histone variants and post-translational modifications that must be finely orchestrated to promote the DNA topological change and compaction provided by the deposition of protamines. That this major transition may not be genetically inert came from early observations that transient DNA strand breaks were detected in situ at chromatin remodeling steps. The potential for genetic instability was later emphasized by our demonstration that a significant number of DNA double-strand breaks (DSBs) are formed and then repaired in the haploid context of spermatids. The detection of DNA breaks by 3′OH end labeling in the whole population of spermatids suggests that a reversible enzymatic process is involved, which differs from canonical apoptosis. We have set the stage for a better characterization of the genetic impact of this transition by showing that post-meiotic DNA fragmentation is conserved from human to yeast, and by providing tools for the initial mapping of the genome-wide DSB distribution in the mouse model. Hence, the molecular mechanism of post-meiotic DSB formation and repair in spermatids may prove to be a significant component of the well-known male mutation bias. Based on our recent observations and a survey of the literature, we propose that the chromatin remodeling in spermatids offers a proper context for the induction of de novo polymorphism and structural variations that can be transmitted to the next generation.
Highlights
As one can appreciate from this Special Issue, the proper packaging of the male haploid genome involves finely-regulated molecular events, resulting in a near complete replacement of somatic chromatin and the formation of a highly condensed nucleus
In haploid cells, copy number variation (CNV) may result from nonhomologous end joining (NHEJ), but can be generated by non-allelic homologous recombination (NAHR) [76], since NAHR is produced by the alignment and subsequent crossover between nonallelic DNA sequence repeats sharing a homology
Given the non-templated DNA repair in haploid spermatids, transient double-strand breaks (DSBs) formation may represent an important component of the male mutation bias and the etiology of neurological disorders, adding to the genetic variation provided by meiosis
Summary
As one can appreciate from this Special Issue, the proper packaging of the male haploid genome involves finely-regulated molecular events, resulting in a near complete replacement of somatic chromatin and the formation of a highly condensed nucleus. Direct methods were used by our group to show that transient post-meiotic DSBs form in the fission yeast, lending strong support to the highly conserved nature of this mechanism [16]. Despite their transient character, the formation of DSBs in the haploid context of spermatids represents a genetic threat, because repair must rely solely on end joining processes, as outlined below [17,18]. Considering the lower DNA repair activity reported in condensing spermatids, potential misprocessing of these DSBs would be expected to further increase genetic instability
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