title: Role of deoxyribonucleic acid polymerase epsilon in spermatogenesis in mice.
abstract: Previous studies on DNA polymerase epsilon indicate that this enzyme is involved in replication of chromosomal DNA. In this study, we examined the expression of DNA polymerases alpha, delta, and epsilon during mouse testis development and germ cell differentiation. The steady-state levels of mRNAs encoding DNA polymerase epsilon and the recombination enzyme Rad51 remained constant during testis development, whereas the mRNA levels of DNA polymerases alpha and delta declined from birth until sexual maturity. Immunohistochemical staining methods, using a stage-specific model of the seminiferous epithelium, revealed dramatic differences between DNA polymerase alpha and epsilon distribution. As expected, DNA polymerase alpha and proliferating cell nuclear antigen showed relatively strong immunostaining in mitotically proliferating spermatogonia and even stronger staining in preleptotene cells undergoing meiotic DNA replication. The distribution of Rad51 was similar, but there was a dramatic peak in late pachytene cells. In contrast, DNA polymerase epsilon was detectable in mitotically proliferating spermatogonia but not in the early stages of meiotic prophase. However, DNA polymerase epsilon reappeared in late pachytene cells and remained through the two meiotic divisions, and was present in haploid spermatids up to the stage at which the flagellum starts developing. Overall, the results suggest that DNA polymerase epsilon functions in mitotic replication, in the completion of recombination in late pachytene cells, and in repair of DNA damage in round spermatids. In contrast, DNA polymerases alpha and delta appear to be involved in meiotic DNA synthesis, which occurs early in meiotic prophase, in addition to functioning in DNA replication in proliferating spermatogonia.
authors.affiliation: Biocenter Oulu and Department of Biochemistry, University of Oulu, Finland.
authors.forename: D
authors.initials: D
authors.lastname: Kamel
authors.forename: Z B
authors.initials: ZB
authors.lastname: Mackey
authors.forename: T
authors.initials: T
authors.lastname: Sjöblom
authors.forename: C A
authors.initials: CA
authors.lastname: Walter
authors.forename: J R
authors.initials: JR
authors.lastname: McCarrey
authors.forename: L
authors.initials: L
authors.lastname: Uitto
authors.forename: H
authors.initials: H
authors.lastname: Palosaari
authors.forename: J
authors.initials: J
authors.lastname: Lähdetie
authors.forename: A E
authors.initials: AE
authors.lastname: Tomkinson
authors.forename: J E
authors.initials: JE
authors.lastname: Syväoja
mesh_terms: D000818:Animals; D004256:DNA Polymerase I / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D004257:DNA Polymerase II / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004258:DNA Polymerase III / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000032:analysis; D015870:Gene Expression; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051135:Rad51 Recombinase; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012670:Seminiferous Epithelium / Q000166:cytology; D013091:Spermatogenesis / Q000502:physiology*; D013094:Spermatozoa / Q000201:enzymology* / Q000502:physiology; D013737:Testis / Q000166:cytology / Q000254:growth & development*
chemical_list: D004268:DNA-Binding Proteins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C495151:RAD51 protein, S cerevisiae; D051135:Rad51 Recombinase; C495154:Rad51 protein, mouse; D004256:DNA Polymerase I; D004257:DNA Polymerase II; D004258:DNA Polymerase III