PT  - JOURNAL ARTICLE
AU  - Supawat Thongthip
AU  - Brooke A. Conti
AU  - Francis P. Lach
AU  - Agata Smogorzewska
TI  - Suppression of non-homologous end joining does not rescue DNA repair defects in Fanconi anemia patient cells
AID  - 10.1101/151472
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 151472
4099  - http://biorxiv.org/content/early/2017/06/17/151472.short
4100  - http://biorxiv.org/content/early/2017/06/17/151472.full
AB  - Severe cellular sensitivity and aberrant chromosomal rearrangements in response to DNA interstrand crosslink (ICL) inducing agents are hallmarks of Fanconi anemia (FA) deficient cells. These phenotypes have previously been ascribed to inappropriate activity of non-homologous end joining (NHEJ) rather than a direct consequence of DNA ICL repair defects. Here we used chemical inhibitors, RNAi, and Clusterd Regularly Interspaced Short Palindromic Repeat (CRISPR)-Cas9 to inactivate various components of NHEJ in cells from FA patients. We show that suppression of DNA-PKcs, DNA Ligase IV and 53BP1 is not capable of rescuing ICL-induced proliferation defects and only 53BP1 knockout partially suppresses the chromosomal abnormalities of FA patient cells.