Send to

Choose Destination
Oncotarget. 2017 Dec 17;9(3):3779-3793. doi: 10.18632/oncotarget.23375. eCollection 2018 Jan 9.

Reduced recruitment of 53BP1 during interstrand crosslink repair is associated with genetically inherited attenuation of mitomycin C sensitivity in a family with Fanconi anemia.

Author information

Laboratory "Genome Dynamics in The Immune System", INSERM UMR1163, Université Paris Descartes Sorbonne Paris Cité, Institut Imagine, Paris, France.
Departement d'Hémato-Oncologie, Hôpital Universitaire des Enfants Reine Fabiola, Bruxelles, Belgium.
Service de Pédiatrie Générale, Centre Hospitalier De Luxembourg, Luxembourg.
INSERM U944, Institut Universitaire d'Hématologie, Paris, France.
Department of Human Genetics and Department of Experimental Medicine, McGill University, Montreal, Canada.
Centre d'Ingénierie Génétique Murine, Institut Pasteur, Paris, France.


The Fanconi anemia (FA) pathway is implicated in the repair of DNA interstrand crosslinks (ICL). In this process, it has been shown that FA factors regulate the choice for DNA double strand break repair towards homologous recombination (HR). As this mechanism is impaired in FA deficient cells exposed to crosslinking agents, an inappropriate usage of non-homologous end joining (NHEJ) leads to the accumulation of toxic chromosomal abnormalities. We studied a family with two FANCG patients and found a genetically inherited attenuation of mitomycin C sensitivity resulting in-vitro in an attenuated phenotype for one patient or in increased resistance for two healthy relatives. A heterozygous mutation in ATM was identified in these 3 subjects but was not directly linked to the observed phenotype. However, the attenuation of ICL sensitivity was associated with a reduced recruitment of 53BP1 during the course of ICL repair, and increased HR levels. These results further demonstrate the importance of favoring HR over NHEJ for the survival of cells challenged with ICLs.


53BP1; ATM; DNA double strand break repair; DNA interstrand crosslinks; Fanconi anemia

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center