MOF-mediated acetylation of Lamin A/C is essential for the maintenance of nuclear architecture and genomic stability in mammalian cells.

The nuclear lamina constitutes more than a structural scaffold for the nucleus and plays a crucial role for genomic integrity. Here we report that loss of the lysine acetyl-transferase (KAT) MOF lead to nuclear lamina architecture defects, including micronuclei formation. We identify Lamin A/C, a nuclear lamina component, as an acetylation target of MOF in vivo. An acetylation deficient Lamin A phenocopies the nuclear aberrations observed upon Mof-deletion and the genomic instability events such as chromothripsis. Our work establishes MOF-dependent Lamin acetylation as a key regulator of nuclear architecture maintenance and genomic integrity.