PSF3 recruits Polθ to stalled replication forks to promote DNA repair
5 affiliations
- 1Fels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140
- 2Department of Chemistry, College of Science and Technology, Temple University, Philadelphia, PA 19122
- 3Cancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, PA 19111
- 4Department of Cancer and Cellular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140
- 5Nuclear Dynamics and Cancer Program, Fox Chase Cancer Center, Philadelphia, PA 19111
Abstract
DNA polymerase theta (Polθ) plays a pivotal role in the maintenance of stalled replication forks. However, little is known about how Polθ is recruited to the stalled forks. Here we show that PSF3, a member of GINS replicative complex, recruits Polθ to the stalled replication forks. Polθ, which is recruited by interacting with the C-terminal portion of PSF3, restarts the forks, exerts DNA double-strand break end-joining to repair the breaks resulting from collapsed forks in BRCA1/2-deficient and proficient tumor cells, and also fills single-stranded gaps on the replication fork lagging strand in BRCA1/2-deficient tumor cells. Thus, PSF3–Polθ interaction promotes the proliferation of homologous recombination-deficient and proficient tumor cells. Overall, this study highlights an important mechanism of Polθ recruitment to the stalled replication forks to maintain Polθ-dependent fork protection in tumor cells.
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BibTeX
@article{vekariya2026psf3,
title = {{PSF3 recruits Polθ to stalled replication forks to promote DNA repair}},
author = {Umeshkumar Vekariya and Benjamin Lee Prather and Roland L. Dunbrack and Rongsheng E. Wang and Tomasz Skorski},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2613699123},
url = {https://doi.org/10.1073/pnas.2613699123},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - PSF3 recruits Polθ to stalled replication forks to promote DNA repair
AU - Umeshkumar Vekariya
AU - Benjamin Lee Prather
AU - Roland L. Dunbrack
AU - Rongsheng E. Wang
AU - Tomasz Skorski
PY - 2026
DA - 2026/10/20
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2613699123
UR - https://doi.org/10.1073/pnas.2613699123
AB - DNA polymerase theta (Polθ) plays a pivotal role in the maintenance of stalled replication forks. However, little is known about how Polθ is recruited to the stalled forks. Here we show that PSF3, a member of GINS replicative complex, recruits Polθ to the stalled replication forks. Polθ, which is recruited by interacting with the C-terminal portion of PSF3, restarts the forks, exerts DNA double-strand break end-joining to repair the breaks resulting from collapsed forks in BRCA1/2-deficient and proficient tumor cells, and also fills single-stranded gaps on the replication fork lagging strand in BRCA1/2-deficient tumor cells. Thus, PSF3–Polθ interaction promotes the proliferation of homologous recombination-deficient and proficient tumor cells. Overall, this study highlights an important mechanism of Polθ recruitment to the stalled replication forks to maintain Polθ-dependent fork protection in tumor cells.
SN - 0027-8424
SN - 1091-6490
ER -