DNA topoisomerase II is dispensable for oocyte meiotic resumption but is essential for meiotic chromosome condensation and separation in mice.
During mitosis, DNA topoisomerase II (TOP2) is required for sister chromatid separation. When TOP2 activity is inhibited, a decatenation checkpoint is activated by entangled chromatin. However, the functions of TOP2 in oocyte meiosis, particularly for homologous chromosome segregation during meiosis I, have not been investigated. In addition, it remains unknown if TOP2 inhibition activates a decatenation checkpoint at the G2/M transition in oocytes. In this study, we used mouse oocytes and specific inhibitors of TOP2 (ICRF-193 and etoposide) to investigate the role of TOP2 in meiosis. Our results indicated that an effective decatenation checkpoint did not exist in fully grown oocytes, as oocytes underwent the G2/M transition and reinitiated meiosis even when TOP2 activity was inhibited. However, oocytes treated with ICRF-193 had severe defects in chromosome condensation and homologous chromosome separation. Furthermore, condensed chromosomes failed to maintain their normal configurations in matured oocytes that were treated with ICRF-193. However, sister chromatid separation and subsequent chromosome decondensation during the exit from meiosis were not blocked by TOP2 inhibitors. These results indicated that TOP2 had a specific, crucial function in meiosis I. Thus, we identified important functions of TOP2 during oocyte maturation and provided novel insights into the decatenation checkpoint during meiosis.
Life Sciences Institute, Zhejiang University, Hangzhou, China.
Xiao-Meng
XM
Li
Chao
C
Yu
Zhong-Wei
ZW
Wang
Yin-Li
YL
Zhang
Xiao-Man
XM
Liu
Dawang
D
Zhou
Qing-Yuan
QY
Sun
Heng-Yu
HY
Fan
D000818:Animals; D002478:Cells, Cultured; D020090:Chromosome Segregation / Q000187:drug effects / Q000235:genetics; D033481:Chromosomes, Mammalian / Q000187:drug effects / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000502:physiology*; D054659:Diketopiperazines; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D059471:In Vitro Oocyte Maturation Techniques; D008297:Male; D008540:Meiosis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D009866:Oogenesis / Q000187:drug effects / Q000235:genetics; D010879:Piperazines / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology
D054659:Diketopiperazines; D010879:Piperazines; D059005:Topoisomerase II Inhibitors; C070899:4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione; D005047:Etoposide; D004250:DNA Topoisomerases, Type II
DNA topoisomerase II; ICRF-193; chromosome condensation and separation; decatenation checkpoint; oocyte maturation