dna lyrics

Localization to DNA damage sites

An alternative model where the integrity of the BRCA1 RING-E2 interaction is important for the correct positioning of the BARD1 BUDR for H2AK13/15ub recognition. Such a function for the BRCA1 RING in enabling ubiquitylated nucleosome binding is further supported with our observation that mutation of the acidic patch-interacting K70/R71 residues also impairs BRCA1 recruitment to DNA lesions in the absence of RAP80. However, we note that in a recent cryo-EM structure of the BRCA1-BARD1 complex bound to unmodified nucleosomes, the E2 is tilted away from the nucleosome and does not appear to participate in nucleosome binding (Witus et al., 2021).

Furthermore, the phenotypic impact of the I26A mutation is much greater than that of the K70A/R71A mutation, which does not align as well with how these mutations impair interaction with nucleosomes and instead follows more closely how these mutations impact BRCA1/BARD1 E3 ligase activity. These two models have testable hypotheses that will be the focus of future experiments