Figure 2.

Overview of how physical, chemical, and biological conditions influence the usage of different DNA repair mechanisms. (A) The choice of DNA repair is tightly controlled by cell cycle. C-NHEJ is activated throughout cell cycles but dominates in G1 phase. TMEJ/MMEJ, SSA and HR are mainly functional from S to G2 phase, while HR becomes more dominant after early S phase when sister chromatids are available as repair templates (Bhargava et al. 2016). The thickness of the lines indicates the activity of different DNA repair pathway in the cell cycle. (B) Local chromatin status affects the choice of DNA repair pathway. For example, TMEJ has been found toward H3K27me3 involved heterochromatin from Schep et al. 2021. The positive or negative roles of H3K36me2/me3 in regulating C-NHEJ, HR or TMEJ has also been reported in multiple studies (Fnu et al. 2011 and Pfister et al. 2014). Besides, uniquely unmethylated lysine residues H4K20me0 on new histones deposited during DNA replication promotes HR repair (Saredi et al. 2016). (C) Nuclear compartments and nuclear positioning are associated with DNA repair patterns. For example, to avoid ectopic recombination, DSB inside heterochromatin relocates to nuclear periphery to induce the error-free HR repair (Ryu et al. 2015), while heterochromatic DSB arising from nuclear lamina remains positionally stable, promotes TMEJ and C-NHEJ and impairs HR (Lemaitre et al. 2014). (D and E) Sequence content and physical chromosome location have influence on DSB repairs. The influence of repeated DNA on HR-mediated genome variation has also been reported (Argueso et al.2008). We propose that repeated DNA might promote to HR, TMEJ/MMEJ and SSA due to the usage of homologous DNA in these repairs. Additionally, it has been found that sub-telomere DSB suffers more from TMEJ/MMEJ and HR than C-NHEJ (Ricchetti et al. 2003, Muraki et al. 2015). These factors do not function alone, but interact to influence DNA repair pathway choice, indicated by arrows between the panels.