Common fragile sites are characterised by faulty condensin loading after replication stress
Boteva, L.; Nozawa, R.-S.; Naughton, C.; Samejima, K.; Earnshaw, W.; Gilbert, N.
Show abstract
Cells coordinate interphase to mitosis transition but recurrent cytogenetic lesions appear at common fragile sites (CFSs) in a tissue-specific manner following replication stress, marking regions of instability in cancer. Despite such a distinct defect no model fully explains their molecular configuration. We show that CFSs are characterised by impaired chromatin folding manifested as disrupted mitotic structures visible using molecular FISH probes in the presence and absence of replication stress. Chromosome condensation assays reveal that compaction-resistant chromatin lesions persist at CFSs throughout the cell cycle and mitosis. Subsequently cytogenetic and molecular lesions arise due to faulty condensin loading at CFSs, through a defect in condensin I mediated compaction and are coincident with mitotic DNA synthesis (MIDAS). This model suggests that in conditions of exogenous replication stress, aberrant condensin loading leads to molecular defects and CFS formation, concomitantly providing an environment for MIDAS, which, if not resolved, result in chromosome instability.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The RAD51 recombinase protects mitotic chromatin in human cells 97%
- PCNA ubiquitination protects stalled replication forks from DNA2-mediated degradation by regulating Okazaki fragment maturation and chromatin assembly 96%
- Poly(ADP-ribose) glycohydrolase promotes formation and homology-directed repair of meiotic DNA double-strand breaks independent of its catalytic activity 95%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.