The recruitment of ACF1 and SMARCA5 to DNA lesions relies on ADP-ribosylation dependent chromatin unfolding

Pinto, Eva and Smith, Rebecca and Bigot, Nicolas and Chapuis, Catherine and Timinszky, Gyula and Huet, Sébastien (2024) The recruitment of ACF1 and SMARCA5 to DNA lesions relies on ADP-ribosylation dependent chromatin unfolding. MOLECULAR BIOLOGY OF THE CELL, 35 (3). ISSN 1059-1524

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Abstract

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.

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