The Fanconi anaemia gene FANCC promotes homologous recombination and error-prone DNA repair

Authors:
Niedzwiedz W, Mosedale G, Johnson M, Ong CY, Pace P and Patel KJ
In:
Mol Cell (2004) 15(4): 607-620
Cells used in publication:
DT40
Species: chicken
Tissue Origin: blood
Abstract
The Fanconi anemia (FA) protein FANCC is essential for chromosome stability in vertebrate cells, a feature underscored by the extreme sensitivity of FANCC-deficient cells to agents that crosslink DNA. However, it is not known how this FA protein facilitates the repair of both endogenously acquired and mutagen-induced DNA damage. Here, we use the model vertebrate cell line DT40 to address this question. We discover that apart from functioning in homologous recombination, FANCC also promotes the mutational repair of endogenously generated abasic sites. Moreover in these vertebrate cells, the efficient repair of crosslinks requires the combined functions of FANCC, translesion synthesis, and homologous recombination. These studies reveal that the FA proteins cooperate with key mutagenesis and repair processes that enable replication of damaged DNA.