|Author||Vo N, Anh Suong DN, Yoshino N, Yoshida H, Cotterill S, Yamaguchi M.|
|Title||Novel roles of HP1a and Mcm10 in DNA replication, genome maintenance and photoreceptor cell differentiation.|
|Journal||Nucleic Acids Res|
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.
|MeSH||Animals Animals, Genetically Modified Cell Differentiation / genetics Cell Differentiation / physiology Chromosomal Proteins, Non-Histone / antagonists & inhibitors Chromosomal Proteins, Non-Histone / genetics* Chromosomal Proteins, Non-Histone / metabolism* DNA Polymerase II / chemistry DNA Polymerase II / genetics DNA Polymerase II / metabolism DNA Replication DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Drosophila Proteins / antagonists & inhibitors Drosophila Proteins / genetics* Drosophila Proteins / metabolism* Drosophila melanogaster / cytology Drosophila melanogaster / genetics Drosophila melanogaster / metabolism Eye / cytology Eye / growth & development Eye / metabolism Female G1 Phase Cell Cycle Checkpoints / genetics G1 Phase Cell Cycle Checkpoints / physiology Gene Expression Regulation, Developmental Gene Knockdown Techniques Genome, Insect Male Microscopy, Electron, Scanning Minichromosome Maintenance Proteins / antagonists & inhibitors Minichromosome Maintenance Proteins / genetics* Minichromosome Maintenance Proteins / metabolism* Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism Nuclear Proteins / genetics Nuclear Proteins / metabolism Photoreceptor Cells, Invertebrate / cytology* Photoreceptor Cells, Invertebrate / metabolism* Recombinant Proteins / genetics Recombinant Proteins / metabolism Replication Protein C / genetics Replication Protein C / metabolism Transcription Factors / genetics Transcription Factors / metabolism|
|WOS Category||BIOCHEMISTRY & MOLECULAR BIOLOGY|
|DNA material||pET16b-fullMCM10-His (RDB15202) pET16b-fullHP1a-His (RDB15203) pFN18A-MCM10-Halo (RDB15204) pFN18A-MCM10-N-term-Halo (RDB15205) pFN18A-MCM10-Linker1-Halo (RDB15206) pFN18A-MCM10-ID-term-Halo (RDB15207) pFN18A-MCM10-Linker2-Halo (RDB15208) pFN18A-HP1a-Halo (RDB15210) pFN18A-HP1a-Chromo-Halo (RDB15211) pFN18A-HP1a-Shadow-Halo (RDB15212).|