PMID:21966530

Citation	Dronamraju, R and Mason, JM (2011) MU2 and HP1a regulate the recognition of double strand breaks in Drosophila melanogaster. PLoS ONE 6:e25439
Abstract	Chromatin structure regulates the dynamics of the recognition and repair of DNA double strand breaks; open chromatin enhances the recruitment of DNA damage response factors, while compact chromatin is refractory to the assembly of radiation-induced repair foci. MU2, an orthologue of human MDC1, a scaffold for ionizing radiation-induced repair foci, is a widely distributed chromosomal protein in Drosophila melanogaster that moves to DNA repair foci after irradiation. Here we show using yeast 2 hybrid screens and co-immunoprecipitation that MU2 binds the chromoshadow domain of the heterochromatin protein HP1 in untreated cells. We asked what role HP1 plays in the formation of repair foci and cell cycle control in response to DNA damage. After irradiation repair foci form in heterochromatin but are shunted to the edge of heterochromatic regions an HP1-dependent manner, suggesting compartmentalized repair. Hydroxyurea-induced repair foci that form at collapsed replication forks, however, remain in the heterochromatic compartment. HP1a depletion in irradiated imaginal disc cells increases apoptosis and disrupts G2/M arrest. Further, cells irradiated in mitosis produced more and brighter repair foci than to cells irradiated during interphase. Thus, the interplay between MU2 and HP1a is dynamic and may be different in euchromatin and heterochromatin during DNA break recognition and repair.
Links	PubMed PMC3179522 Online version:10.1371/journal.pone.0025439
Keywords	Animals; Apoptosis/genetics; Apoptosis/physiology; Cell Cycle/genetics; Cell Cycle/physiology; Chromosomal Proteins, Non-Histone/genetics; Chromosomal Proteins, Non-Histone/metabolism; DNA Breaks, Double-Stranded; DNA Repair/genetics; DNA Repair/physiology; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster; Immunoprecipitation; Two-Hybrid System Techniques
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
DROME:HP1		GO:0007067: mitosis	ECO:0000314:		P		Fig 7. Treatment of S2 cells with HP1a dsRNA leads to a decrease in the number of cells in S phase and an apparent increase in the number of cells at both G1 and G2/M.	complete CACAO 2115
DROME:HP1		GO:0000792 : heterochromatin	ECO:0000314:		C		Figure 1. Interaction of MU2 and HP1a.	complete CACAO 2103
DROME:HP1	involved_in	GO:0000278: mitotic cell cycle	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
DROME:HP1		GO:0005701: polytene chromosome chromocenter	ECO:0000315:		C		Figure 3. Effects of HP1a depletion on focal movement.	complete CACAO 2108
DROME:HP1		GO:0010369: chromocenter	ECO:0000314:		C		Figure 4. HP1a is not recruited to IRIF and laser induced breaks.	complete CACAO 2110

References

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