title: Cre-mediated recombination can induce apoptosis in vivo by activating the p53 DNA damage-induced pathway.
abstract: Cre-mediated apoptosis has been observed in many contexts in mice expressing Cre-recombinase and can confound the analysis of genetically engineered conditional mutant or transgenic alleles. Several mechanisms have been proposed to explain this phenomenon. We find that the degree of apoptosis induced correlates roughly with the copy number of loxP sites present in the genome and that some level of increased apoptosis accompanies the presence of even only a few loxP sites, as occurs in conditional floxed alleles. Cre-induced apoptosis in this context is completely p53-dependent, suggesting that the apoptosis is stimulated by p53 activation in response to DNA damage incurred during the process of Cre-mediated recombination.
authors.affiliation: Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI-Frederick, Frederick, Maryland 21702, USA.
authors.forename: Jianjian
authors.initials: J
authors.lastname: Zhu
authors.forename: Minh-Thanh
authors.initials: MT
authors.lastname: Nguyen
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Nakamura
authors.forename: Junming
authors.initials: J
authors.lastname: Yang
authors.forename: Susan
authors.initials: S
authors.lastname: Mackem
mesh_terms: D000483:Alleles; D000818:Animals; D017209:Apoptosis; D004249:DNA Damage; D018628:Gene Dosage; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011995:Recombination, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D025521:Tumor Suppressor Proteins; C045073:Cre recombinase; D019426:Integrases