Posttranslační modifikace v buněčné odpovědi na poškození DNA

Moudrý, Pavel

Our genetic material is continually challenged by varieties of factors and processes that represent enormous threat to our ability to transmit genetic information to our offspring and to our survival as well. Cells possess many mechanisms capable of detecting and repairing damaged DNA, collectively known as DNA damage response (DDR). DDR activities must be tightly regulated in a spatiotemporal and DNA lesion-specific manner to optimize repair and prevent alterations in DNA during normal cellular processes. Defects in DNA repair drive genomic instability and may ultimately lead to cancer and neurodegenerative diseases. This work is a compilation of 4 projects focused on molecular mechanisms of DNA damage response and assembly of multiprotein signalling and repair complexes at sites of DNA damage. We identified nuclear pore component NUP153 as a novel factor specifically required for 53BP1 nuclear import and DDR. We showed that NUP153 knockdown prevents 53BP1 from entering the nuclei in newly forming daughter cells, which translates to decreased IR-induced 53BP1 foci formation, delayed DNA repair, impaired survival after IR and exacerbates replication stress-induced DNA damage. Furthermore, we identified ubiquitin-activating enzyme UBA1 as the apical E1 enzyme required for response to IR and replication...

guest :: login Digital Repository
		Search		Submit		Help		About