Novel roles of HP1a and Mcm10 in DNA replication, genome maintenance and photoreceptor cell differentiation.
Both Mcm10 and HP1a are known to be required for DNA replication. However, underlying mechanism is not clarified yet especially for HP1. Knockdown of both HP1a and Mcm10 genes inhibited the progression of S phase in Drosophila eye imaginal discs. Proximity Ligation Assay (PLA) demonstrated that HP1a is in close proximity to DNA replication proteins including Mcm10, RFC140 and DNA polymerase ε 255 kDa subunit in S-phase. This was further confirmed by co-immunoprecipitation assay. The PLA signals between Mcm10 and HP1a are specifically observed in the mitotic cycling cells, but not in the endocycling cells. Interestingly, many cells in the posterior regions of eye imaginal discs carrying a double knockdown of Mcm10 and HP1a induced ectopic DNA synthesis and DNA damage without much of ectopic apoptosis. Therefore, the G1-S checkpoint may be affected by knockdown of both proteins. This event was also the case with other HP family proteins such as HP4 and HP6. In addition, both Mcm10 and HP1a are required for differentiation of photoreceptor cells R1, R6 and R7. Further analyses on several developmental genes involved in the photoreceptor cell differentiation suggest that a role of both proteins is mediated by regulation of the lozenge gene.
Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan.|The Center for Advanced Insect Research, Kyoto Institute of Technology, Kyoto, Japan.
Nicole
N
Vo
Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan.|The Center for Advanced Insect Research, Kyoto Institute of Technology, Kyoto, Japan.
Dang Ngoc
DN
Anh Suong
Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan.|The Center for Advanced Insect Research, Kyoto Institute of Technology, Kyoto, Japan.
Natsuki
N
Yoshino
Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan.|The Center for Advanced Insect Research, Kyoto Institute of Technology, Kyoto, Japan.
Hideki
H
Yoshida
Department of Basic Medical Sciences, St Georges, University of London, London, UK.
Sue
S
Cotterill
Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan.|The Center for Advanced Insect Research, Kyoto Institute of Technology, Kyoto, Japan.
Masamitsu
M
Yamaguchi
D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D004257:DNA Polymerase II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D005123:Eye / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D049750:Genome, Insect; D008297:Male; D008855:Microscopy, Electron, Scanning; D064110:Minichromosome Maintenance Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D051818:Replication Protein C / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C489612:MCM10 protein, Drosophila; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; C099964:lz protein, Drosophila; C073099:pros protein, Drosophila; D000090266:Chromobox Protein Homolog 5; D004257:DNA Polymerase II; D051818:Replication Protein C; D064110:Minichromosome Maintenance Proteins