title: Local DNA underreplication correlates with accumulation of phosphorylated H2Av in the Drosophila melanogaster polytene chromosomes.
abstract: DNA in Drosophila melanogaster polytene chromosomes is known to be locally underreplicated in both pericentric and intercalary heterochromatin. When the SuUR gene is mutant, complete and partial suppression of underreplication are observed in intercalary and pericentric heterochromatin, respectively; in contrast, overexpression of SuUR results in stronger underreplication. Using antibodies against phosphorylated histone H2Av and flies with different levels of SuUR expression, we demonstrated a clear correlation between the extent of underreplication in specific chromosome regions and the accumulation of H2Av phosphorylated at S137 (gamma-H2AX) at the same sites. Phosphorylated H2Av is a well-established marker of DNA double-stranded breaks (DSB). Our data thus argue that DNA underreplication leads to DSBs and that DSBs accumulate as salivary gland cells progress throughout repeated endocycles. We speculate that ligation of free double-stranded DNA termini causes the formation of ectopic contacts between the underreplicated regions in heterochromatin.
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, 630090, Russia.
authors.forename: E N
authors.initials: EN
authors.lastname: Andreyeva
authors.forename: T D
authors.initials: TD
authors.lastname: Kolesnikova
authors.forename: E S
authors.initials: ES
authors.lastname: Belyaeva
authors.forename: R L
authors.initials: RL
authors.lastname: Glaser
authors.forename: I F
authors.initials: IF
authors.lastname: Zhimulev
mesh_terms: D000818:Animals; D000906:Antibodies; D002875:Chromosomes / Q000378:metabolism*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000737:chemistry; D029721:Drosophila Proteins / Q000737:chemistry; D004331:Drosophila melanogaster / Q000378:metabolism*; D005260:Female; D006570:Heterochromatin; D006657:Histones / Q000378:metabolism*; D007814:Larva / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport
chemical_list: D000906:Antibodies; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006570:Heterochromatin; D006657:Histones; D010750:Phosphoproteins; C464850:SuUR protein, Drosophila