Regulation of the female mouse germ cell cycle during entry into meiosis.
During mouse embryonic development germ cells proliferate extensively until they commit to the male or female pathway and arrest in mitosis or meiosis respectively. Whilst the transition of female germ cells exiting the mitotic cell cycle and entering meiosis is well defined histologically, the essential cell cycle proteins involved in this process have remained unresolved. Using flow cytometry we have examined the entry of female germ cells into meiosis, their termination of DNA synthesis and entry into prophase I. Analysis of key G(2)/M cell cycle proteins revealed that entry into meiosis and cell cycle exit at G(2)/M involves repression of G(2)/M promoting Cyclin B1, coincident upregulation of G(2)/M repressing Cyclin B3 and robust establishment of the ATM/CHK2 pathway. By contrast we show that the ATR/CHK1 pathway is activated in male and female germ cells. This data indicates that an important G(2)/M surveillance mechanism operates during germ cell proliferation and that passage into meiotic G(2)/M involves the combined repression of G(2)/M through Cyclin B3 and activation of the key G(2)/M checkpoint regulatory network modulated through ATM and CHK2. This work shows that the core regulatory machinery that controls G(2)/M progression in mitotic cells is activated in female mouse germ cells as they enter meiosis.
Miles
Denise C
DC
Murdoch Childrens Research Institute, Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, VIC, Australia.
van den Bergen
Jocelyn A
JA
Sinclair
Andrew H
AH
Western
Patrick S
PS
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D019926:Cyclin B / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D016195:G2 Phase; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008540:Meiosis; D051379:Mice; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D018797:Cell Cycle Proteins; D019926:Cyclin B; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; C576897:Atr protein, mouse; D064447:Checkpoint Kinase 2; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D000071877:Checkpoint Kinase 1; C000605869:Chek1 protein, mouse; C578633:Chek2 protein, mouse; D017346:Protein Serine-Threonine Kinases