Protection of nascent DNA at stalled replication forks is mediated by phosphorylation of RIF1 intrinsically disordered region

• DOI: 10.7554/elife.75047
• Publication Date: 2022-04-13T13:00:22Z
• Authors: Sandhya Balasubra...; Matteo Andreani; Júlia Goncalves A...; Tannishtha Saha; Devakumar Sundara...; Javier Garzón; Wenzhu Zhang; Oliver Popp; Shin-ichiro Hiraga; Ali Rahjouei; Daniel B Rosen; Philipp Mertins; Brian T Chait; Anne D Donaldson; Michela Di Virgilio
• Keywords: Replication protein A; Origin recognition complex; Nuclease

RIF1 is a multifunctional protein that plays key roles in the regulation of DNA processing. During repair double-strand breaks (DSBs), functions 53BP1-Shieldin pathway inhibits resection ends to modulate cellular decision on which engage. Under conditions replication stress, protects nascent at stalled forks from degradation by DNA2 nuclease. How these activities are regulated post-translational level has not yet been elucidated. Here, we identified cluster conserved ATM/ATR consensus SQ motifs within intrinsically disordered region (IDR) mouse phosphorylated proliferating B lymphocytes. We found phosphorylation IDR dispensable for inhibition DSB RIF1, but essential counteract DNA2-dependent forks. Therefore, our study identifies molecular feature enables genome-protective function during stress.