Expression and possible functions of DNA lesion bypass proteins in spermatogenesis

Abstract

In mammalian cells, there is a complex interplay of different DNA damage response and repair mechanisms. Several observations suggest that, in particular in gametogenesis, proteins involved in DNA repair play an intricate role in and outside the context of DNA repair. Here, we discuss the possible roles of proteins that take part in replicative damage bypass (RDB) mechanisms, also known as post-replication DNA repair (PRR), in germ line development. In yeast, and probably also in mammalian somatic cells, RDB [two subpathways: damage avoidance and translesion synthesis (TLS)] prevents cessation of replication forks during the S phase of the cell cycle, in situations when the replication machinery encounters a lesion present in the template DNA. Many genes encoding proteins involved in RDB show an increased expression in testis, in particular in meiotic and post-meiotic spermatogenic cells. Several RDB proteins take part in protein ubiquitination, and we address relevant aspects of the ubiquitin system in spermatogenesis. RDB proteins might be required for damage avoidance and TLS of spontaneous DNA damage during gametogenesis. In addition, we consider the possible functional relation between TLS and the induction of mutations in spermatogenesis. TLS requires the activity of highly specialized polymerases, and is an error-prone process that may induce mutations. In evolutionary terms, controlled generation of a limited number of mutations in gametogenesis might provide a mechanism for evolvability.