Abstract：
:Mutations in citron (CIT), leading to loss or inactivation of the citron kinase protein (CITK), cause primary microcephaly in humans and rodents, associated with cytokinesis failure and apoptosis in neural progenitors. We show that CITK loss induces DNA damage accumulation and chromosomal instability in both mammals and Drosophila. CITK-deficient cells display "spontaneous" DNA damage, increased sensitivity to ionizing radiation, and defective recovery from radiation-induced DNA lesions. In CITK-deficient cells, DNA double-strand breaks increase independently of cytokinesis failure. Recruitment of RAD51 to DNA damage foci is compromised by CITK loss, and CITK physically interacts with RAD51, suggesting an involvement of CITK in homologous recombination. Consistent with this scenario, in doubly CitK and Trp53 mutant mice, neural progenitor cell death is dramatically reduced; moreover, clinical and neuroanatomical phenotypes are remarkably improved. Our results underscore a crucial role of CIT in the maintenance of genomic integrity during brain development.
journal_name
Cell Repjournal_title
Cell reportsauthors
Bianchi FT,Tocco C,Pallavicini G,Liu Y,Vernì F,Merigliano C,Bonaccorsi S,El-Assawy N,Priano L,Gai M,Berto GE,Chiotto AM,Sgrò F,Caramello A,Tasca L,Ala U,Neri F,Oliviero S,Mauro A,Geley S,Gatti M,Di Cunto Fdoi
10.1016/j.celrep.2017.01.054subject
Has Abstractpub_date
2017-02-14 00:00:00pages
1674-1686issue
7issn
2211-1247pii
S2211-1247(17)30111-0journal_volume
18pub_type
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