Date of Award
Doctor of Philosophy in Biological and Environmental Sciences
Cell and Molecular Biology (CMB)
Cell & Molecular Biology
Fanconi anemia (FA) is a rare genetic disease that results on early onset bone marrow failure, congenital defects, and increased cancer susceptibility. It is caused by mutation in any one of twenty two genes, whose protein products work in conjunction as part of the FA-BRCA pathway, a DNA repair pathway that specifically repairs DNA interstrand crosslinks (ICLs). One of the key steps in pathway activation is the monoubiquitination of the FANCD2 protein. Upon pathway activation, FANCD2 is recruited to sites of DNA damage, where is interacts with downstream repair protiens to promote DNA repair via homologous recombination (HR). How FANCD2 recognizes DNA damage in condensed compact chromatin, however, has remained unknown. Here, we uncover a FANCD2 methyl-binding domain, which specifically binds for H4K20me2 in order to recruit FANCD2 to sites on DNA damage and promote homologous recombination, support cell survival and maintain genomic integrity.
Paquin, Karissa Lynn, "Characterization of a H4K20ME2 Methyl-Binding Domain in the Fanconi Anemia Protein FANCD2" (2017). Open Access Dissertations. Paper 648.
Available for download on Wednesday, November 20, 2019