CEP152 is a genome maintenance protein disrupted in Seckel syndrome

OpenAlex İngilizce

Bernd Wollnik and colleagues report mutations in CEP152 cause Seckel syndrome, which is characterized by short stature, severe microcephaly and mental retardation. The work suggests that CEP152 has a function in genome maintenance. Functional impairment of DNA damage response pathways leads to increased genomic instability. Here we describe the centrosomal protein CEP152 as a new regulator of genomic integrity and cellular response to DNA damage. Using homozygosity mapping and exome sequencing, we identified CEP152 mutations in Seckel syndrome and showed that impaired CEP152 function leads to accumulation of genomic defects resulting from replicative stress through enhanced activation of ATM signaling and increased H2AX phosphorylation.