A team of researchers from the Department of Biology and Biotechnology "Charles Darwin" of Sapienza and the Pasteur Institute Italy - Cenci Bolognetti Foundation used combined reverse genetics, cell biology and biochemistry approach to assess the role and involvement of the SRCAP protein in cell cycle progression (in HeLa cells), in relation to Floating-Harbor syndrome. The study results, published in the journal BMC Biology, identify the SRCAP protein as a central factor in the development of this rare disease.

Several human genetic diseases are caused by mutations encoding for epigenetic chromatin factors and regulators. Floating-Harbor syndrome, also known as Pelletier-Leisti syndrome, is a very rare genetic syndrome that alters human development and is caused by dominant mutations in the SRCAP gene, which encodes the eponymous ATPase-functioning protein required for chromatin remodelling. The syndrome is characterised by delayed bone mineralisation and insufficient growth, often associated with intellectual disability and skeletal and craniofacial abnormalities.

Why is the SRCAP protein so important? Because of the role this protein plays in epigenetic regulation, it is generally believed that the Floating-Harbor syndrome is caused by profound chromatin perturbations.

"Surprisingly, however, we found that the SRCAP protein associates with components of the mitotic apparatus (centrosomes, spindle and midbody), interacts with a plethora of cytokinesis regulators and positively regulates their recruitment to the midbody, a bridge structure that determines the correct cleavage of daughter cells in the cytokinesis phase"- says Patrizio Dimitri of Sapienza, work coordinator.

Lack of SRCAP in cultured human cells alters cell division at both the mitotic and terminal stages of cytokinesis, as shown in the study for the orthologous protein in the model organism Drosophila melanogaster.

"These results represent the first experimental evidence for an evolutionarily conserved role of SRCAP in the control of cell division, independent of its chromatin regulatory function. We hypothesise that SRCAP is involved in two different phases: in mitosis, by ensuring proper chromosome segregation; in cytokinesis, by contributing to the proper functioning of the midbody" - concludes Dimitri.

The research thus shows that alterations in cell division induced by SRCAP mutations may contribute to the onset of Floating-Harbor syndrome.

References:

The ATPase SRCAP is associated with the mitotic apparatus, uncovering novel molecular aspects of Floating-Harbor syndrome - Giovanni Messina, Yuri Prozzillo, Francesca Delle Monache, Maria Virginia Santopietro, Maria Teresa Atterrato & Patrizio Dimitri - BMC Biol. 2021 DOI: 10.1186/s12915-021-01109-x

Further Information

Patrizio Dimitri
Department of Biology and Biotechnology "Charles Darwin"
patrizio.dimitri@uniroma1.it