The recruitment of ACF1 and SMARCA5 to DNA lesions relies on ADP-ribosylation dependent chromatin unfolding
ADP-ribosylation signaling orchestrates the recruitment of various repair actors and chromatin remodeling processes promoting access to lesions during the early stages of the DNA damage response. The chromatin remodeler complex ACF, composed of the ATPase subunit SMARCA5/SNF2H and the cofactor ACF1/BAZ1A, is among the factors that accumulate at DNA lesions in an ADP-ribosylation dependent manner. In this work, we show that each subunit of the ACF complex accumulates to DNA breaks independently from its partner. Furthermore, we demonstrate that the recruitment of SMARCA5 and ACF1 to sites of damage is not due to direct binding to the ADP-ribose moieties but due to facilitated DNA binding at relaxed ADP-ribosylated chromatin. Therefore, our work provides new insights regarding the mechanisms underlying the timely accumulation of ACF1 and SMARCA5 to DNA lesions, where they contribute to efficient DNA damage resolution.
The ACF chromatin remodeling complex is involved in DNA repair. Here, we investigate the mechanisms underlying the recruitment of ACF to DNA lesions.
We show that ACF1 and SMARCA5, the subunits of the ACF complex, recruit to DNA lesions independently of each other. Furthermore, we find that their ADPr-dependent accumulation to the lesions does not rely on binding to ADP-ribose but rather on the facilitated access to DNA at relaxed ADPr-ribosylated chromatin.
Our work highlight how ADP-ribose dependent chromatin remodeling contributes to efficient DNA repair by promoting the recruitment of the ACF complex to DNA lesions.