Cyclin A1-deficient mice lack histone H3 serine 10 phosphorylation and exhibit altered aurora B dynamics in late prophase of male meiosis

摘要

MalemicelackingcyclinA1proteinaresterile.Theirsterilityresultsfromanarrestinthemeioticcellcycleofspermatocytes,whichwenowidentifyasoccurringatlatediplotene,immediatelybeforediakinesis.ThestageofarrestincyclinA1-deficientmiceisdistinctfromthearrestseeninspermatocytesthataredeficientinitsputativecatalyticpartnerCdk2,whichoccursmuchearlierinpachytene.ThearrestincyclinA1-deficientspermatocytesisalsoaccompaniedbyanunusualclusteringofcentromericheterochromatin.Consistentwithapossibledefectinthecentromericregion,immunofluorescentstainingofcyclinA1proteinshowslocalizationintheregionofthecentromere.PhosphorylationofhistoneH3atserine10inpericentromericheterochromatin,whichnormallyoccursinlatediplotene,isreducedinspermatocytesfromheterozygousemCcna1/emsupem+//emminus;/suptestesandcompletelyabsentinspermatocyteswithnocyclinA1protein.Concomitantly,thelevelsofpericentromericauroraBkinase,knowntophosphorylatehistoneH3duringmeiosis,arepartiallyreducedinspermatocytesfromtestesofheterozygousmiceandfurtherreducedinhomozygousnullspermatocytes.Thesedatasuggestacriticalandconcentration-dependentfunctionforcyclinA1inthepericentromericregioninlatediploteneofmeiosis,perhapsinassemblyorfunctionofthepassengerproteincomplex./p/div