Biology subjects

Santa Rosa, P.

Publications and source records attributed to Santa Rosa, P..

2 recordsLinked to original sources

bioRxiv2026

Altering dosage of meiotic crossover-associated RING finger proteins affects crossover number and interference in Drosophila

Crossovers play a critical role in ensuring correct reductional segregation of homologous chromosomes in the first meiotic division. Crossing over is initiated by formation of DNA double-strand breaks (DSBs), but the number of DSBs is greater than the number of crossovers. Which recombination sites become crossovers, versus being repaired as non-crossovers, is not random, but is subject to several crossover patterning phenomena, including crossover assurance and crossover interference. One current model for crossover designation proposes that crossover-associated RING finger proteins (CORs) undergo the biophysical process of coarsening, in which larger accumulations continue to get larger and smaller accumulations go away. Genetic and cytological studies of the three CORs in Drosophila melanogaster, Vilya, Narya, and Nenya, are consistent with this model. In females heterozygous for a deletion of vilya, fewer doublecrossovers are observed. Conversely, crossovers are elevated in females carrying a duplication of vilya and in females coordinately overexpressing Vilya, Narya, and Nenya. These findings support a model in which crossover designation occurs through coarsening of COR proteins within the synaptonemal complex.

genetics↗

bioRxiv2022

Distinct developmental phenotypes result from mutation of Set8/KMT5A and histone H4 lysine 20 in Drosophila melanogaster

Mono-methylation of histone H4 lysine 20 (H4K20me1) is catalyzed by Set8/KMT5A and regulates numerous aspects of genome organization and function. Loss-of-function mutations in Drosophila melanogaster Set8 or mammalian KMT5A prevent H4K20me1 and disrupt development. Set8/KMT5A also has non-histone substrates, making it difficult to determine which developmental functions of Set8/KMT5A are attributable to H4K20me1 and which to other substrates or to non-catalytic roles. Here, we show that human KMT5A can functionally substitute for Set8 during Drosophila development and that the catalytic SET domains of the two enzymes are fully interchangeable. We also uncovered a role in eye development for the N-terminal domain of Set8 that cannot be complemented by human KMT5A. Whereas Set8null mutants are inviable, we found that an R634G mutation in the SET domain predicted to ablate catalytic activity resulted in viable adults, suggesting important non-catalytic functions of Set8. Similarly, flies that were engineered to express only unmodifiable H4 histones (H4K20A) can also complete development, but they are phenotypically distinct from H4K20R, Set8null, and Set8R634G animals. Taken together, our results demonstrate functional conservation of KMT5A and Set8 enzymes, as well as distinct roles for Set8 and H4K20me1 in Drosophila development.

genetics↗