A novel Ku70 function in colorectal homeostasis separate from nonhomologous end joining.

ABSTRACT: Ku70, a known nonhomologous end-joining (NHEJ) factor, also functions in tumor suppression, although this molecular mechanism remains uncharacterized. Previously, we showed that mice deficient for DNA ligase IV (Lig4), another key NHEJ factor, succumbed to aggressive lymphoma in the absence of tumor suppressor p53. However, the tumor phenotype is abrogated by the introduction of a hypomorphic mutant p53(R172P), which impaired p53-mediated apoptosis but not cell-cycle arrest. However, Lig4(-/-)p53(R172P) mice succumbed to severe diabetes. To further elucidate the role of NHEJ and p53-mediated apoptosis in vivo, we bred Ku70(-/-) p53(R172P) mice. Unexpectedly, these mice were free of diabetes, although 80% of the mutant mice had abnormally enlarged colons with pronounced inflammation. Remark

SUBMITTER: Puebla-Osorio N 

PROVIDER: S-EPMC5761319 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature