Pendolino, a gene affecting the stability of Drosophila heterochromatic telomeres
Drosophilatelomeres are sequence-independent structures that are maintained by transposition to chromosome ends of specialized retroelements rather than telomerase activity. Fly telomeres are capped by the terminin complex that localizes and function exclusively at telomeres and by a number of non-terminin proteins that do not serve telomere-specific functions. pendolino (peo), encodes a non-terminin protein homologous to the E2 variant ubiquitin-conjugating enzymes. Null peo mutants exhibit ~ 5 telomeric fusions (TFs) per cell. We have identified a viable hypomorphic allele of peo (peoh) that causes ~ 1 TF/cell; 99% of the TFs observed in this allele involve the heterochromatic telomeres (the Y, XR and 4th chromosome telomeres), a TF pattern never observed in the telomere capping mutants so far characterized, where all telomeres fuse with comparable frequencies. This suggests thatheterochromatic telomeres are preferentially affected by Peo reduction and that this effect is masked in null mutants in which most telomeres are fused. We found that peo mutants exhibit a general defect in DNA replication, suggesting that the peculiar TF pattern of these mutants could reflect specific problems in heterochromatin replication at the end of the S phase. We also found that larvae homozygous for peoh and heterozygous for either Su(var)3-9 or Su(var)2-5 (HP1) exhibit a strong increase in the TF frequency compared to peoh/peoh single mutants. In contrast, larvae homozygous for peoh and heterozygous for a mutation in the Jil-1 kinase-coding gene exhibit a substantial reduction in TFs compared to peoh/peoh single mutants. Su(var)3-9 specifically trimethylates K9 of histone H3 facilitating Su(var)205/HP1 recruitment and leading to “compact/repressive” heterochromatin; in contrast, Jil-1phosphorylates S10 of the same histone leading to “open” heterochromatin. Our results are consistent with the antagonistic roles of Su(var)3-9/HP1 and Jil-1, and implicate for the first time histone modifications in Drosophila telomere protection.