Germline TP53 mutations result into a constitutive defect of p53 DNA binding and transcriptional response to DNA damage.

ABSTRACT: Li-Fraumeni Syndrome (LFS) results from heterozygous germline mutations of TP53, encoding a key transcriptional factor activated in response to DNA damage. We have recently shown, from a large LFS series, that dominant-negative missense mutations are the most clinically severe and, thanks to a new p53 functional assay in lymphocytes, that they alter the p53 transcriptional response to DNA damage more drastically than null mutations. In this study, we first confirmed this observation by performing the p53 functional assay in lymphocytes from 56 TP53 mutation carriers harbouring 35 distinct alterations. Then, to compare the impact of the different types of germline TP53 mutations on DNA binding, we performed chromatin immunoprecipitation-sequencing (ChIP-Seq) in lymphocytes exposed to doxoru

SUBMITTER: Zerdoumi Y 

PROVIDER: S-EPMC5886078 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature