Functional Organization of the Genome Group

The packaging of genomic DNA into chromatin profoundly influences nuclear processes such as transcription, replication, repair and recombination. Understanding how chromatin structure modulates the expression and maintenance of the information encoded in eukaryotic genomes, and how these processes take place within the context of a highly complex and compacted genomic chromatin environment is one of the major basic questions in biology.

 To tackle this question we will employ a variety of genetic systems with impaired chromatin structure and address the replicative, transcriptional, and DNA damage responses to these altered chromatin scenarios with a combination of state-of-the-art approaches from single-molecule to genome-wide analysis. We recently found that perturbations in the integrity of the chromatin template elicit a range of responses in the dynamics of DNA replication and transcription, with different consequences on replicative stress (Almeida et al., 2018. Nat Commun 9: 1590). These findings have broad implications for our understanding of how defects in chromatin structure, such as those occurring during cellular aging or in some developmental disorders or cancer, contribute to genomic instability.