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Analysis of expression and function of topoisomerase I and II during meiosis in male mice
Author(s) -
Cobb John,
Reddy Rajashekar K.,
Park Cynthia,
Handel Mary Ann
Publication year - 1997
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/(sici)1098-2795(199704)46:4<489::aid-mrd7>3.0.co;2-k
Subject(s) - prophase , biology , topoisomerase , meiosis , metaphase , synaptonemal complex , microbiology and biotechnology , chromatin , genetics , premature chromosome condensation , teniposide , chromosome , gene , dna , etoposide , chemotherapy
Topoisomerases are nuclear enzymes that remove torsional stress in DNA. Their function is important for replication, transcription, chromosome condensation, and chromosome segregation during mitosis and meiosis. The goal of this work is to analyze both expression and function of topoisomerases during the meiotic stages of mammalian spermatogenesis. The patterns of expression of topoisomerase I and topoisomerase IIα genes were followed on Northern blots of RNA from testes of mice of different ages and from specific germ cell populations. The transcript of the topoisomerase I gene was highest in somatic cells of the testis and in the mitotically proliferating spermatogonia and meiotic prophase spermatocytes, with the level of transcript decreasing dramatically in postmeiotic spermatids. In contrast, the levels of topoisomerase IIα transcript were negligible in germcell free testes and highest in late meiotic prophase cells and round spermatids. Enzyme activity for both topoisomerase I and topoisomerase II was detected in both pachytene spermatocytes and in round spermatids; topoisomerase II exhibited a higher level of activity in meiotic spermatocytes than in round spermatids. In cultured cells, camptothecin, an inhibitor of topoisomerase I, caused some abnormalities of paired meiotic homologs, but did not inhibit the transition to metaphase. In contrast, teniposide and ICRF‐193, inhibitors of topoisomerase II, dramatically inhibited the formation of metaphase chromosomes in cells induced to progress from prophase to metaphase. However, the disassembly of the synaptonemal complex was not inhibited, indicating that this process could be uncoupled from condensation of chromatin to form chromosomes. These studies constitute evidence for a functional requirement for topoisomerase II activity in the transition from meiotic prophase to meiotic metaphase I in mammalian spermatocytes. Mol. Reprod. Dev. 46:489–498, 1997. © 1997 Wiley‐Liss, Inc.