| Title: |
Protection of nascent DNA at stalled replication forks is mediated by phosphorylation of RIF1 intrinsically disordered region |
| Authors: |
Sandhya Balasubramanian; Matteo Andreani; Júlia Goncalves Andrade; Tannishtha Saha; Devakumar Sundaravinayagam; 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 |
| Source: |
eLife, Vol 11 (2022) |
| Publisher Information: |
eLife Sciences Publications Ltd, 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Medicine; LCC:Science; LCC:Biology (General) |
| Subject Terms: |
RIF1; SQ motifs; intrinsically disordered region; DSB resection inhibition; DNA replication fork protection; Medicine; Science; Biology (General); QH301-705.5 |
| Description: |
RIF1 is a multifunctional protein that plays key roles in the regulation of DNA processing. During repair of DNA double-strand breaks (DSBs), RIF1 functions in the 53BP1-Shieldin pathway that inhibits resection of DNA ends to modulate the cellular decision on which repair pathway to engage. Under conditions of replication stress, RIF1 protects nascent DNA at stalled replication forks from degradation by the DNA2 nuclease. How these RIF1 activities are regulated at the post-translational level has not yet been elucidated. Here, we identified a cluster of conserved ATM/ATR consensus SQ motifs within the intrinsically disordered region (IDR) of mouse RIF1 that are phosphorylated in proliferating B lymphocytes. We found that phosphorylation of the conserved IDR SQ cluster is dispensable for the inhibition of DSB resection by RIF1, but is essential to counteract DNA2-dependent degradation of nascent DNA at stalled replication forks. Therefore, our study identifies a key molecular feature that enables the genome-protective function of RIF1 during DNA replication stress. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2050-084X |
| Relation: |
https://elifesciences.org/articles/75047; https://doaj.org/toc/2050-084X |
| DOI: |
10.7554/eLife.75047 |
| Access URL: |
https://doaj.org/article/9aa8a2536f2d4d70bc4fcafdfdb0c33a |
| Accession Number: |
edsdoj.9aa8a2536f2d4d70bc4fcafdfdb0c33a |
| Database: |
Directory of Open Access Journals |