Genes, Vol. 11, Pages 326: Impaired Replication Timing Promotes Tissue-Specific Expression of Common Fragile Sites

Genes, Vol. 11, Pages 326: Impaired Replication Timing Promotes Tissue-Specific Expression of Common Fragile Sites Genes doi: 10.3390/genes11030326 Authors: Klizia Maccaroni Elisa Balzano Federica Mirimao Simona Giunta Franca Pelliccia Common fragile sites (CFSs) are particularly vulnerable regions of the genome that become visible as breaks, gaps, or constrictions on metaphase chromosomes when cells are under replicative stress. Impairment in DNA replication, late replication timing, enrichment of A/T nucleotides that tend to form secondary structures, the paucity of active or inducible replication origins, the generation of R-loops, and the collision between replication and transcription machineries on particularly long genes are some of the reported characteristics of CFSs that may contribute to their tissue-specific fragility. Here, we validated the induction of two CFSs previously found in the human fetal lung fibroblast line, Medical Research Council cell strain 5 (MRC-5), in another cell line derived from the same fetal tissue, Institute for Medical Research-90 cells (IMR-90). After induction of CFSs through aphidicolin, we confirmed the expression of the CFS 1p31.1 on chromosome 1 and CFS 3q13.3 on chromosome 3 in both fetal lines. Interestingly, these sites were found to not be fragile in lymphocytes, suggesting a role for epigenetic or transcriptional programs for this tissue specificity. Both these sites contained late-replicating genes NEGR1 (neuro...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Article Source Type: research