MAU2-independent loading of cohesin and a protective mechanism against early truncating mutations in NIPBL

Investigating a NIPBL early truncating mutation we observe that MAU2 and the NIPBL N-terminus are largely dispensable for normal cohesin and NIPBL functioning. In cells with thepredicted fatal out-of-frame single nucleotide duplication c.39dup in NIPBL the use of an alternative translation initiation site yields expression of an N-terminally truncated NIPBL that cannot interact with MAU2 and dramatically reduced MAU2 levels. Remarkably, this protective mechanism allows nearly normal amounts of cohesin to be loaded onto chromatin and we observe only small changes in gene expression.