Ferrari
Fakultäten » Medizinische Fakultät » Molekulare Krebsforschung, Institut für » Prof. Dr. Josef Jiricny » Ferrari
Completed research project
| Title / Titel | Regulation of DNA mismatch repair by phosphorylation: a cell division cycle perspective | ||
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| Abstract (PDF, 14 KB) | |||
| Summary / Zusammenfassung | Damage to the genetic material is potentially catastrophic to cells, particularly when they are in the process of replicating the DNA. DNA damage can be caused by exogenous chemical or physical agents, such as inhaled cigarette smoke, ultraviolet light or incompletely defined dietary factors. However, it is becoming evident that a large fraction of DNA lesions can also result from endogenous metabolic processes. Damage to the genetic material is sensed by checkpoint pathways that generate signals delaying the onset of mitosis, the ultimate goal of this process being maintenance of genome stability. The study outlined below will attempt to shed light on the cross talk between DNA damage sensors and pathways controlling transition through the cell cycle. In particular, this study will address the possibility that components of the machinery that detects and corrects mismatched bases in DNA are regulated by phosphorylation. Focus of the analysis will be the protein kinases regulating transition through the cell division cycle (Cyclin-dependent kinases or CDKs) and kinases directly involved in the DNA-damage response. With regard to the former and considering that the mismatch repair (MMR) machinery is a post-replication repair system, particular emphasis will be put on the Cdks active during transition through S-phase. The DNA-damage activated kinases that will be examined in this study are Casein-kinase 2 (CK2) and the p38 mitogen-activated protein kinase (p38MAPK). The initial phase of the proposed study will aim at the identification of the sites of phosphorylation in MMR proteins whereas in a second phase the role of phosphorylation on the regulation of MMR activity will be investigated. |
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| Keywords / Suchbegriffe | cell cycle, DNA damage response, mismatch repair, phosphorylation | ||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Funding source(s) / Unterstützt durch |
SNF (Personen- und Projektförderung) |
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| In collaboration with / In Zusammenarbeit mit |
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| Duration of Project / Projektdauer | May 2004 to Apr 2006 |