SLX4–XPF mediates DNA damage responses to replication stress induced by DNA–protein interactions

• DOI: 10.1083/jcb.202003148
• Publication Date: 2020-12-21T16:36:55Z
• Authors: Riko Ishimoto; Yota Tsuzuki; Tomoki Matsumura; Seiichiro Kurashige; Kouki Enokitani; Koki Narimatsu; Mitsunori Higa; Nozomi Sugimoto; Kazumasa Yoshida; Masatoshi Fujita
• Keywords: Replication

The DNA damage response (DDR) has a critical role in the maintenance of genomic integrity during chromosome replication. However, responses to replication stress evoked by tight DNA-protein complexes have not been fully elucidated. Here, we used bacterial LacI protein binding lacO arrays make site-specific fork barriers on human chromosome. These induced accumulation single-stranded (ssDNA) and various DDR proteins at site. SLX4-XPF functioned as an upstream factor for proteins, consequently, ATR FANCD2 were interdependently recruited. Moreover, S phase caused underreplication abnormal mitotic segregation arrays. Finally, show that SLX4-ATR axis represses anaphase abnormality binding. Our results outline long-term process which cells manage nucleoprotein obstacles ahead prevent chromosomal instability.