Defective DNA Repair in Spermiogenesis

The histone-to-protamine exchange process in spermatids (chromatin remodeling) offers a window for DNA vulnerability whereby both endogenous and exogenous factors can induce damage. Transient DNA strand breaks have been shown to be part of the differentiation program of these cells likely to help relieve the torsional stress from nucleosome eviction. As they include a significant proportion of double-strand breaks (DSBs), DNA repair in this haploid context may not be templated and rely solely on end-joining mechanisms. Evidence of active nonhomologous DNA repair mechanisms in spermatids are accumulating and are described here, since they are known to be error-prone and potentially mutagenic. These DSBs may be created by the action of type II topoisomerases or from mechanical constrains. The surge in DSBs and subsequent repair implies that an efficient repair mechanism must be operating despite that condensing proteins in spermatids may represent an impediment to this process. Insertion and deletions are expected to be created from the repair of mechanical or enzyme-induced breaks. Interestingly, from an evolutionary standpoint, the lower reliability of the repair process could also be considered as a mechanism to generate more diversity. Several exogenous factors, including reactive oxygen species and chemotherapy, may also alter the DNA damage response and are briefly outlined.