Úloha a význam FANCD2 proteinu

Bc. Veronika Altmannová, Ph.D.

Master's thesis

Fanconi Anemia:The role of FANCD2 protein

Abstract:

Fanconi anemia belongs to a group of rare human genetic diseases and is frequently associated with bone marrow failure, high predisposition to cancer and birth defects. The cells from Fanconi anemia’s patients are hypersensitive to crosslinking agents (e.g. diepoxybutane or mitomycin C), and show an increased frequency of chromosome breakage. To date, thirteen complementations groups (FANCA, -B, -C, -D1, -D2, -E, -F, -G, -I, -J, -L, -M, and –N) have been associated with Fanconi anemia. It has been also demonstrated that all proteins encoded by FA genes cooperate in common pathway, called as FA or FA/BRCA pathway. After DNA damage or during S-phase, eight FA proteins (A, B, C, E, F, G, L, and M) asssemble in a multisubunit nuclear complex (FA core complex), which is required for monoubiquitination of FANCD2 at lysine 561. The monoubiquitinated isoform of FANCD2 is targeted to DNA damage-induced nuclear foci where it colocalizes and interacts with other proteins participating in DNA repair, such as BRCA1, RAD51 and BRCA2 (also identified as FANCD1). The exact role of FANCD2 is still unknown and hence it is the major goal of this thesis to better elucidate its biological function, thereby to further the understanding of the whole machinery of FA pathway.

Keywords

Fanconi anemia, FANCD2 protein, FA pathway, SUMOylation, DNA binding

Language used: English

Date on which the thesis was submitted / produced: 24. 5. 2007

Thesis defence

• Date of defence: 8. 6. 2007
• Supervisor: doc. Mgr. Lumír Krejčí, Ph.D.

Masaryk University

Faculty of Science

Master programme / field:
Biochemistry / Biochemistry