Ricerc@Sapienza

The nuclear envelope compartmentalizes chromatin in eukaryotic cells. The main nuclear envelope components are lamins that associate with a panoply of factors, including the LEM domain
proteins. The nuclear envelope of mammalian cells opens up during cell division. It is reassembled
and associated with chromatin at the end of mitosis when telomeres tether to the nuclear
periphery. Lamins, LEM domain proteins, and DNA binding factors, as BAF, contribute to the
reorganization of chromatin. In this context, an emerging role is that of the ESCRT complex, a

Human AKTIP and mouse Ft1 are orthologous ubiquitin E2 variant proteins involved in telomere maintenance and DNA replication. AKTIP also interacts with A- and B-type lamins. These features suggest that Ft1 may be implicated in aging regulatory pathways. Here, we show that cells derived from hypomorph Ft1 mutant (Ft1kof/kof ) mice exhibit telomeric defects and that Ft1kof/kof animals develop progeroid traits, including impaired growth, skeletal and skin defects, abnormal heart tissue, and sterility. We also demonstrate a genetic interaction between Ft1 and p53.