Role of the DNA damage signalling and repair pathways in the prevention of tumorigenesis and neurodegeneration in the central nervous system

点击翻译按钮获取中文摘要

The integrity of DNA inside cells is constantly being challenged by endogenous and exogenous DNA-damaging agents. Stability of genomic DNA organization is fundamental to the faithful transmission of genetic information and the prevention of carcinogenesis. The developing nervous system exhibits a high sensitivity to DNA damage and in particularly to DNA double-strand breaks (DSBs). In nervous system, DNA DSBs trigger a cascade of signalling events that lead to repair and resolution of the break, or as is very frequent, apoptosis. Additionally the importance of DSBs repair to the central nervous system (CNS) is illustrated by the neurological abnormalities observed in patients with hereditary diseases associated with defects in DSBs repair such as A-T, A-TLD and NBS or Seckel syndrome. The objectives of this research project is to analyse the consequences of inactivation of DNA damage repair/signalling genes on the normal development and neurodegeneration of the central nervous system using mouse models. The research project will be focused on two genes SMC1 (coding for a DNA damage signalling protein) and RINT-1 (coding for a Rad50 interacting protein) that are involved in DNA damage response. This study will allow to acquire a better knowledge about the response of CNS to DNA damage. Ultimately, it will provide new clues to elaborate treatments for brain tumours and neurodegenerative diseases.