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- Title
TFIP11 promotes replication fork reversal to preserve genome stability.
- Authors
Chen, Junliang; Wu, Mingjie; Yang, Yulan; Ruan, Chunyan; Luo, Yi; Song, Lizhi; Wu, Ting; Huang, Jun; Yang, Bing; Liu, Ting
- Abstract
Replication fork reversal, a critical protective mechanism against replication stress in higher eukaryotic cells, is orchestrated via a series of coordinated enzymatic reactions. The Bloom syndrome gene product, BLM, a member of the highly conserved RecQ helicase family, is implicated in this process, yet its precise regulation and role remain poorly understood. In this study, we demonstrate that the GCFC domain-containing protein TFIP11 forms a complex with the BLM helicase. TFIP11 exhibits a preference for binding to DNA substrates that mimic the structure generated at stalled replication forks. Loss of either TFIP11 or BLM leads to the accumulation of the other protein at stalled forks. This abnormal accumulation, in turn, impairs RAD51-mediated fork reversal and slowing, sensitizes cells to replication stress-inducing agents, and enhances chromosomal instability. These findings reveal a previously unidentified regulatory mechanism that modulates the activities of BLM and RAD51 at stalled forks, thereby impacting genome integrity. The RAD51 recombinase plays a pivotal role in replication fork reversal during replication stress. Here, the authors show that the GCFC domain-containing protein TFIP11 interacts with BLM helicase and is important for fork reversal during replication stress to preserve genome stability.
- Subjects
EUKARYOTIC cells; DNA replication; RECOMBINASES; SUGAMMADEX
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-45684-3