Over 300 mutations in the LMNA gene, encoding A-type lamins, are associated with 
15 human degenerative disorders and premature aging syndromes. Although genomic 
instability seems to contribute to the pathophysiology of some laminopathies, 
there is limited information about what mutations cause genomic instability and 
by which molecular mechanisms. Mouse embryonic fibroblasts depleted of A-type 
lamins or expressing mutants lacking exons 8-11 (Lmna(Δ8-11/Δ8-11)) exhibit 
alterations in telomere biology and DNA repair caused by cathepsin L-mediated 
degradation of 53BP1 and reduced expression of BRCA1 and RAD51. Thus, a region 
encompassing exons 8-11 seems essential for genome integrity. Given that 
deletion of lamin A exon 9 in the mouse (Lmna(Δ9/Δ9)) results in a progeria 
phenotype, we tested if this domain is important for genome integrity. 
Lmna(Δ9/Δ9) MEFs exhibit telomere shortening and heterochromatin alterations but 
do not activate cathepsin L-mediated degradation of 53BP1 and maintain 
expression of BRCA1 and RAD51. Accordingly, Lmna(Δ9/Δ9) MEFs do not present 
genomic instability, and expression of mutant lamin A Δexon9 in lamin-depleted 
cells restores DNA repair factors levels and partially rescues nuclear 
abnormalities. These data reveal that the domain encoded by exon 9 is important 
to maintain telomere homeostasis and heterochromatin structure but does not play 
a role in DNA repair, thus pointing to other exons in the lamin A tail as 
responsible for the genomic instability phenotype in Lmna(Δ8-11/Δ8-11) mice. Our 
study also suggests that the levels of DNA repair factors 53BP1, BRCA1 and RAD51 
could potentially serve as biomarkers to identify laminopathies that present 
with genomic instability.