dAdd1 and dXNP prevent genome instability by maintaining HP1a localization at Drosophila telomeres
Telomeres are important contributors to genome stability, as they prevent linear chromosome end degradation and contribute to the avoidance of telomeric fusions. An important component of the telomeres is the heterochromatin protein 1a (HP1a). Mutations in Su(var)205, the gene encoding HP1a in Drosophila, result in telomeric fusions, retrotransposon regulation loss and larger telomeres, leading to chromosome instability. Previously, it was found that several proteins physically interact with HP1a, including dXNP and dAdd1 (orthologues to the mammalian ATRX gene). In this study, we found that mutations in the genes encoding the dXNP and dAdd1 proteins affect chromosome stability, causing chromosomal aberrations, including telomeric defects, similar to those observed in Su(var)205 mutants. In somatic cells, we observed that dXNP and dAdd1 participate in the silencing of the telomeric HTT array of retrotransposons, preventing anomalous retrotransposon transcription and integration. Furthermore, the lack of dAdd1 results in the loss of HP1a from the telomeric regions without affecting other chromosomal HP1a binding sites; mutations in dxnp also affected HP1a localization but not at all telomeres, suggesting a specialized role for dAdd1 and dXNP proteins in locating HP1a at the tips of the chromosomes. These results place dAdd1 as an essential regulator of HP1a localization and function in the telomere heterochromatic domain.
KeywordsATRX HP1a Telomeres HTT array Heterochromatin
We thank Dr. James Mason for providing the GIII strain. We also thank Silvia Meyer for the construction of the plasmids used. We would like to thank Benjamín Hernández for his participation at the beginning of this work. We also thank Claudia Mónica Flores Loyola for her participation in the LOH assay. J.C. was supported by a Masters degree scholarship from the Consejo Nacional de Ciencia y Tecnología (CONACyt, 404495). J.M.M-M was supported by a DGAPA-UNAM postdoctoral fellowship. We also thank Arturo Pimentel, Andrés Saralegui and Dr. Chris Wood from the LMNA for the advice on the use of the microscopes. We thank Dr. Martha Vazquez for her valuable comments on this work. This work was supported by grants from CONACyT 219673 and DGAPA UNAM number IN200315 to MZ and grant 177393 from (CONACyT) and grants IN204915 and IA200613 from (PAPIIT-UNAM) to VV-G.
Compliance with ethical standards
This article does not contain any studies with human participants or animals performed by any of the authors.
Conflict of interest
The authors declare that they have no conflict of interest.
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