Ali Bakr, Giuditta Della Corte, Olivera Veselinov, Simge Kelekçi, Mei-Ju May Chen, Yu-Yu Lin, Gianluca Sigismondo, Marika Iacovone, Alice Cross, Rabail Syed, Yunhee Jeong, Etienne Sollier, Chun-Shan Liu, Pavlo Lutsik, Jeroen Krijgsveld, Dieter Weichenhan, Christoph Plass, Odilia Popanda, Peter Schmezer
AT-rich interaction domain protein 1A (ARID1A), a SWI/SNF chromatin remodeling complex subunit, is frequently mutated across various cancer entities. Loss of ARID1A leads to DNA repair defects. Here, we show that ARID1A plays epigenetic roles to promote both DNA double-strand breaks (DSBs) repair pathways, non-homologous end-joining (NHEJ) and homologous recombination (HR). ARID1A is accumulated at DSBs after DNA damage and regulates chromatin loops formation by recruiting RAD21 and CTCF to DSBs. Simultaneously, ARID1A facilitates transcription silencing at DSBs in transcriptionally active chromatin by recruiting HDAC1 and RSF1 to control the distribution of activating histone marks, chromatin accessibility, and eviction of RNAPII...
April 8, 2024: Nucleic Acids Research