Community Research and Development Information Service - CORDIS



Project ID: 617485
Funded under: FP7-IDEAS-ERC
Country: Netherlands

Mid-Term Report Summary - CHROMATINREPAIRCODE (CHROMATIN-REPAIR-CODE: Hacking the chromatin code for DNA repair)

Our cells receive tens of thousands of different DNA lesions per day. Failure to repair these lesions will lead to cell death, mutations and genome instability, which contribute to human diseases such as neurodegenerative disorders and cancer. Efficient recognition and repair of DNA damage, however, is complicated by the fact that genomic DNA is packaged, through histone and non-histone proteins, into a condensed structure called chromatin. The DNA repair machinery has to circumvent this barrier to gain access to the damaged DNA and repair the lesions. Our recent work suggests that chromatin-modifying enzymes (CME) help to overcome this barrier at sites of DNA damage. However, the identity of these CME, their mode of action and interconnections with DNA repair pathways remain largely enigmatic. The aim of this project is to systematically identify and characterize the CME that operate during DNA repair processes in both yeast and human cells. To reach this goal we used a cross-disciplinary approach that combines novel and cutting-edge genomics approaches with bioinformatics, genetics, biochemistry and high-resolution microscopy. Epigenetics-IDentifier (Epi-ID) has unveiled several CME that induced novel histone modifications to regulate transcription and/or DNA repair in yeast. Moreover, RNAi-interference screens in human cells have uncovered novel CME that may regulate the repair of DNA damage. A series of functional assays is currently being applied to characterize the role of some of the identified CME in distinct DNA repair pathways, focusing on those that counteract DNA strand breaks and replication stress.

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