Fig. 1: Stochastic cell-cycle model of structural variant (SV) generation from DNA repair and replication.
From: Cell-cycle dependent DNA repair and replication unifies patterns of chromosome instability
a Illustration of the cell-cycle model along a branching process. The cell cycle contains interphase and mitosis (M phase), where interphase consists of DNA replication with three phases: G1 (growth) in which the cell grows, S (synthesis) in which the cell replicates DNA, and G2 (growth) in which the cell grows to prepare for mitosis. In G1, the repairing of the broken chromosomes depends on their linear genomic distance and may form chromosome fusion. Some unrepaired double-strand breaks (DSBs) may lead to sister chromatid fusion after DNA replication in S and G2. In M, the chromosomes with one centromere are distributed to each daughter cell and the chromosome without centromere is randomly distributed to a daughter cell. The chromosomes with more than one centromere are randomly broken and distributed to the daughter cells, imitating breakage-fusion-bridge (BFB) which may cause local fragmentation. b The graph representation of a diploid genome. Left, two pairs of normal chromosomes with light colour indicating homologue A and dark colour indicating homologue B. Middle, one homologue of each chromosome is broken at some breakpoints and rejoined randomly. The normal chromosome is represented by two telomeres connected with an interval edge. The broken and repaired chromosome is represented by the joining of both telomeres and breakpoints with interval, reference, and variant edges. Right, the repaired chromosomes with SVs (translocation and inversion). c The accumulation of SVs in two cell cycles starting from a normal cell. Left, the circos plots of all the cells with cell lineage information, where the inner and outer heatmaps within the circle represent copy numbers of homologue A and B respectively. Middle, the haplotype graph of cell 2, where the breakpoints are located at different homologues which are not distinguished in the circos plots. Right, the cell lineage tree and copy numbers of chromosomes with copy number alterations (CNAs). The copy numbers in the two daughter cells after a cell cycle are always reciprocal. DUP-like: tandem duplication-like patterns, DEL-like: deletion-like patterns, H2HINV: head-to-head inversion, T2TINV: tail-to-tail inversion, INTER-CHR: inter-chromosomal SV. Source data are provided as a Source Data file.
