Structure and function of CAD-ICAD proteins

• Thesis title in Czech: Struktura a funkce proteinů CAD-ICAD
• Thesis title in English: Structure and function of CAD-ICAD proteins
• Key words: Apoptóza, Kaspázou aktivovaná DNáza (CAD), Inhibitor kaspázou aktivované DNázy (ICAD), Fragmentace DNA, Fosforylace ICAD
• English key words: Apoptosis, Caspase-activated DNase (CAD), Inhibitor of caspase-activated DNase (ICAD), DNA fragmentation, ICAD phosphorylation
• Academic year of topic announcement: 2024/2025
• Thesis type: Bachelor's thesis
• Thesis language: angličtina
• Department: Department of Genetics and Microbiology (31-140)
• Supervisor: RNDr. Josef Novák, Ph.D.
• Author: Bc. Shakhkhan Nildikeshev - assigned and confirmed by the Study Dept.
• Date of registration: 18.12.2024
• Date of assignment: 18.12.2024
• Confirmed by Study dept. on: 29.01.2025
• Date of electronic submission: 29.04.2025
• Date of proceeded defence: 30.05.2025
• Opponents: RNDr. Zora Nováková, Ph.D.

References

Larsen BD, Benada J, Yung PYK, Bell RAV, Pappas G, Urban V, Ahlskog JK, Kuo TT, Janscak P, Megeney LA, Elsässer SJ, Bartek J, Sørensen CS. Cancer cells use self-inflicted DNA breaks to evade growth limits imposed by genotoxic stress. Science. 2022 Apr 29;376(6592):476-483. doi: 10.1126/science.abi6378. Epub 2022 Apr 28. PMID: 35482866.
Wu C, Zhang Y, Sun Z, Li P. Molecular evolution of Cide family proteins: novel domain formation in early vertebrates and the subsequent divergence. BMC Evol Biol. 2008 May 23;8:159. doi: 10.1186/1471-2148-8-159. PMID: 18500987; PMCID: PMC2426694.
Eckhart L, Fischer H, Tschachler E. Phylogenomics of caspase-activated DNA fragmentation factor. Biochem Biophys Res Commun. 2007 Apr 27;356(1):293-9. doi: 10.1016/j.bbrc.2007.02.122. Epub 2007 Mar 1. PMID: 17343828.
Kulbay M, Bernier-Parker N, Bernier J. The role of the DFF40/CAD endonuclease in genomic stability. Apoptosis. 2021 Feb;26(1-2):9-23. doi: 10.1007/s10495-020-01649-7. Epub 2021 Jan 2. PMID: 33387146.

Preliminary scope of work

Caspase-Activated DNase (CAD) je DNáza zodpovědná za fragmentaci DNA při apoptóze. Regulaci tohoto enzymu zajišťuje Inhibitor of Caspase Activated DNase (ICAD). Bakalářská práce zpracuje literární rešerši funkce a struktury těchto dvou proteinů. Krátce popíše kanonickou apoptotickou funkci těchto proteinů: formování heterodimeru CAD-ICAD, rozštěpení ICAD, formování homodimeru CAD a vyvolání apoptózy. Dále se práce bude věnovat nově popsané nekanonické funkci komplexu CAD-ICAD ve vytváření jednovláknových zlomů DNA (Larsen et al., 2022). Očekávanou součástí práce je také popis evoluce proteinů CAD-ICAD.

Preliminary scope of work in English

Caspase-Activated DNase (CAD) is a DNase responsible for DNA fragmentation during the apoptosis; this process is regulated by Inhibitor of Caspase Activated DNase (ICAD). The bachelor thesis will describe structure and function of these proteins. It will shortly describe canonical apoptotic function of the proteins: formation of CAD-ICAD dimer, proteolytic cleavage of ICAD, formation of CAD dimer and apoptosis. The thesis will then focus on recently described non-canonical function of CAD-ICAD complex in induction of single strand DNA breaks (Larsen et al., 2022). The expected part of the thesis is also description of CAD-ICAD evolution.