COSMOS · The Conformation Of S-phase chroMOSomes

The Conformation Of S-phase chroMOSomes

The organization of DNA within a nucleus is essential for all processes that occur. It’s extremely important for DNA replication and mitotic DNA segregation to occur without excessive entanglements and subsequent DNA damage. Correct organization is also essential for cell functions including transcription, DNA repair and recombination. However, when organization is impaired this can lead to chromosomal aberrations that accompany tumour progression. Extensive organizational structure analyses have been carried out utilizing chromosome conformation capture (Hi-C) methodology which has helped us understand the different orders of compaction of the genome. However, Hi-C is not able to take into account the differences between the exactly identical replicated sister chromatids. How DNA interactions occur between the sisters and throughout the nucleus is therefore not well understood. Newly replicated sister chromatids are held together by a mixture of DNA intertwines and the cohesin complex. As the cell cycle progresses and the DNA must be segregated, sisters are compacted by SMC proteins and disentangled by topoisomerase proteins. The interplay between the proteins and how they act to perfectly disentangle sister chromatids in order to prevent DNA damage in every cell cycle is important for us to be able to understand. Therefore this project aimed to expand techniques that are available to distinguish sister chromatids from one another for chromosome conformation analysis. Then this technique for sister chromatid conformation analysis could be further utilised to answer crucial questions about how the conformation of DNA is controlled to prevent aberrant processes from occurring. This work advances the field of DNA conformation analysis substantially, by developing a technique that will allow wide scale uptake for many different labs to be able to further understand the processes occurring during the cell cycle and how these processes go wrong in disease.

Data: CORDIS, © European Union