TY - JOUR
T1 - FIRRM/C1orf112 is synthetic lethal with PICH and mediates RAD51 dynamics
AU - Stok, Colin
AU - Tsaridou, Stavroula
AU - van den Tempel, Nathalie
AU - Everts, Marieke
AU - Wierenga, Elles
AU - Bakker, Femke J
AU - Kok, Yannick
AU - Alves, Inês Teles
AU - Jae, Lucas T
AU - Raas, Maximilian W D
AU - Huis In 't Veld, Pim J
AU - de Boer, H Rudolf
AU - Bhattacharya, Arkajyoti
AU - Karanika, Eleftheria
AU - Warner, Harry
AU - Chen, Mengting
AU - van de Kooij, Bert
AU - Dessapt, Julien
AU - ter Morsche, Lars
AU - Perepelkina, Polina
AU - Fradet-Turcotte, Amelie
AU - Guryev, Victor
AU - Tromer, Eelco C
AU - Chan, Kok-Lung
AU - Fehrmann, Rudolf S N
AU - van Vugt, Marcel A T M
N1 - Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2023/7/25
Y1 - 2023/7/25
N2 - Joint DNA molecules are natural byproducts of DNA replication and repair. Persistent joint molecules give rise to ultrafine DNA bridges (UFBs) in mitosis, compromising sister chromatid separation. The DNA translocase PICH (ERCC6L) has a central role in UFB resolution. A genome-wide loss-of-function screen is performed to identify the genetic context of PICH dependency. In addition to genes involved in DNA condensation, centromere stability, and DNA-damage repair, we identify FIGNL1-interacting regulator of recombination and mitosis (FIRRM), formerly known as C1orf112. We find that FIRRM interacts with and stabilizes the AAA
+ ATPase FIGNL1. Inactivation of either FIRRM or FIGNL1 results in UFB formation, prolonged accumulation of RAD51 at nuclear foci, and impaired replication fork dynamics and consequently impairs genome maintenance. Combined, our data suggest that inactivation of FIRRM and FIGNL1 dysregulates RAD51 dynamics at replication forks, resulting in persistent DNA lesions and a dependency on PICH to preserve cell viability.
AB - Joint DNA molecules are natural byproducts of DNA replication and repair. Persistent joint molecules give rise to ultrafine DNA bridges (UFBs) in mitosis, compromising sister chromatid separation. The DNA translocase PICH (ERCC6L) has a central role in UFB resolution. A genome-wide loss-of-function screen is performed to identify the genetic context of PICH dependency. In addition to genes involved in DNA condensation, centromere stability, and DNA-damage repair, we identify FIGNL1-interacting regulator of recombination and mitosis (FIRRM), formerly known as C1orf112. We find that FIRRM interacts with and stabilizes the AAA
+ ATPase FIGNL1. Inactivation of either FIRRM or FIGNL1 results in UFB formation, prolonged accumulation of RAD51 at nuclear foci, and impaired replication fork dynamics and consequently impairs genome maintenance. Combined, our data suggest that inactivation of FIRRM and FIGNL1 dysregulates RAD51 dynamics at replication forks, resulting in persistent DNA lesions and a dependency on PICH to preserve cell viability.
U2 - 10.1016/j.celrep.2023.112668
DO - 10.1016/j.celrep.2023.112668
M3 - Article
C2 - 37347663
SN - 2211-1247
VL - 42
JO - Cell reports
JF - Cell reports
IS - 7
M1 - 112668
ER -