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The importance of genomic stability

Faithful replication of genetic material is essential for development and health maintenance. Genome integrity involves not only finely orchestrated reproduction of DNA but also chromatin, its protein packaging framework.
The importance of genomic stability
Recently, research has highlighted the importance of chromatin organisation of DNA working alongside repair pathways to maintain genomic stability. Two processes stand out as really important – the DNA damage repair pathway and accurate chromosomal replication.

The CHRODIGI (Chromatin dynamics in genome integrity) project has worked on the identification of molecules behind the integration of chromatin into the genomic stability network. The scientists also identified interconnections between chromatin regulators and genome stability factors.

Using budding yeast, the researchers looked at two chromatin factors conserved throughout evolution – enzyme INO80 and the histone variant H2A.Z. Both these proteins have been linked to upkeep of genome stability but how they protect its integrity is unclear.

Results demonstrated that at a DNA double strand break, recruitment of chromatin regulators such as INO80 is regulated by cell cycle position. Interestingly, recruitment coincides with reduced levels of H2A.X phosphorylation. H2A.X is a variant of H2A.Z and is active in DNA repair by non-homologous end joining. This work, challenging a central theory on how chromatin is integrated into the DNA damage response was published in Nature Reviews Genetics.

The CHRODIGI team found a connection between INO80 and the nuclear protein degradation network. The results suggest that INO80-mediated nucleosome remodelling through RNA polymerase II (RNAPII) breakdown is required for cell growth during genotoxic stress.

This is the first study to link chromatin regulation to nuclear protein turnover. Project researchers are now planning to investigate the physical and functional interconnection between chromatin and the protein degradation network during DNA metabolism.

Chromosome stability is of crucial significance in cell division and propagation. An abnormal number of chromosome(s) during unbalanced cell separation at cell division is associated with almost all solid tumour cancers. Identification of key factors involved in genetic stability promises to reveal mechanisms that avoid development of diseases.

Related information


Genomic stability, DNA, chromatin, INO80, H2A.Z, solid tumour
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