53BP1 Protects against CtIP-Dependent Capture of Ectopic Chromosomal Sequences at the Junction of Distant Double-Strand Breaks
Fig 5
The “spatiotemporal gap” favors ectopic chromosomal sequences.
A. Close DSEs are immediately tethered and then ligated. Distant DSBs require synapsis to give space and time for dissociation of KU and 53BP1 from DNA ends and for CtIP to intrude and act during this “spatiotemporal gap”. This favors non-conservative events, among them ectopic sequence capture (red). B. Hypothetical model for chromosome sequence capture through micro-homology-mediated template switching (MMts). Upper panel: synapsis of distant DSEs. Lower panels: 1- micro-homology template switching (MMts) without unidentified sequences leading to ectopic chromosomal sequence (ECS) capture (in blue); 2- N-additions (in red) by non-template polymerases 3- successive round of MMTS resulting in unidentified sequences (in red and green) at the borders of inserted sequence. C. Sequence homology-independent microhomologies-mediated unequal sister chromatid exchange through MMts. Blue lines: reporter sequences. Grey sphere: centromere.