Chromosome territory formation attenuates the translocation potential of cells

eLife

Olivia Crocker¹  Son C Nguyen¹  Leah F Rosin¹  Eric F Joyce¹  Randi L Isenhart¹  Zhuxuan Xu¹ 

[1] Department of Genetics, Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States;

关键词: chromosome territory;    Condensin II;    oligopaints;    FISH;    translocation;    genome integrity;   

DOI  :  10.7554/eLife.49553

来源: DOAJ

【 摘 要 】

The formation and spatial arrangement of chromosome territories (CTs) in interphase has been posited to influence the outcome and frequency of genomic translocations. This is supported by correlations between the frequency of inter-chromosomal contacts and translocation events in myriad systems. However, it remains unclear if CT formation itself influences the translocation potential of cells. We address this question in Drosophila cells by modulating the level of Condensin II, which regulates CT organization. Using whole-chromosome Oligopaints to identify genomic rearrangements, we find that increased contact frequencies between chromosomes due to Condensin II knockdown leads to an increased propensity to form translocations following DNA damage. Moreover, Condensin II over-expression is sufficient to drive spatial separation of CTs and attenuate the translocation potential of cells. Together, these results provide the first causal evidence that proper CT formation can protect the genome from potentially deleterious translocations in the presence of DNA damage.

【 授权许可】

Unknown