Figure 1. A model for DSB repair regulation. TOPBP1 is rapidly recruited to the DNA damage site through its interaction with the 9-1-1 complex. 53BP1 (Rad9 in yeast) and BRCA1 compete for binding the TOPBP1 scaffold protein at DSB. ATR (Mec1 in yeast) enhances BRCA1 interaction with TOPBP1 (Liu et al., 2017). 53BP1 phosphorylation by ATM promotes the recruitment of RIF1 and PTIP, which blocks end resection, thereby promoting NHEJ. CDK phosphorylates PALB2 and inhibits the BRCA1–PALB2 interaction. At the resected end, ATR promotes the BRCA1–PALB2 interaction by phosphorylating PALB2 in conjunction with CDK inhibition, which facilitates BRCA2-dependent HR (Buisson et al., 2017). BRCA1 counteracts NHEJ by promoting PP4-dependent dephosphorylation of 53BP1, which results in RIF1 release (Isono et al., 2017).
Figure 1.

A model for DSB repair regulation. TOPBP1 is rapidly recruited to the DNA damage site through its interaction with the 9-1-1 complex. 53BP1 (Rad9 in yeast) and BRCA1 compete for binding the TOPBP1 scaffold protein at DSB. ATR (Mec1 in yeast) enhances BRCA1 interaction with TOPBP1 (Liu et al., 2017). 53BP1 phosphorylation by ATM promotes the recruitment of RIF1 and PTIP, which blocks end resection, thereby promoting NHEJ. CDK phosphorylates PALB2 and inhibits the BRCA1–PALB2 interaction. At the resected end, ATR promotes the BRCA1–PALB2 interaction by phosphorylating PALB2 in conjunction with CDK inhibition, which facilitates BRCA2-dependent HR (Buisson et al., 2017). BRCA1 counteracts NHEJ by promoting PP4-dependent dephosphorylation of 53BP1, which results in RIF1 release (Isono et al., 2017).

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