@article{7f598a97988d4f22a7f6e400056d91f5,
title = "MIF is a 3{\textquoteright} flap nuclease that facilitates DNA replication and promotes tumor growth",
abstract = "How cancer cells cope with high levels of replication stress during rapid proliferation is currently unclear. Here, we show that macrophage migration inhibitory factor (MIF) is a 3{\textquoteright} flap nuclease that translocates to the nucleus in S phase. Poly(ADP-ribose) polymerase 1 co-localizes with MIF to the DNA replication fork, where MIF nuclease activity is required to resolve replication stress and facilitates tumor growth. MIF loss in cancer cells leads to mutation frequency increases, cell cycle delays and DNA synthesis and cell growth inhibition, which can be rescued by restoring MIF, but not nuclease-deficient MIF mutant. MIF is significantly upregulated in breast tumors and correlates with poor overall survival in patients. We propose that MIF is a unique 3{\textquoteright} nuclease, excises flaps at the immediate 3{\textquoteright} end during DNA synthesis and favors cancer cells evading replication stress-induced threat for their growth.",
author = "Yijie Wang and Yan Chen and Chenliang Wang and Mingming Yang and Yanan Wang and Lei Bao and Wang, {Jennifer E.} and Kim, {Bong Woo} and Chan, {Kara Y.} and Weizhi Xu and Emanuela Capota and Janice Ortega and Deepak Nijhawan and Li, {Guo Min} and Weibo Luo and Yingfei Wang",
note = "Funding Information: We thank Dr. W. Lee Kraus for providing pTY-U6-hPAPR1 plasmid, Dr. Elliott Ross for the helpful discussion on MIF kinetics analysis and the UTSW proteomic Core for mass spectrometry analysis. This work was supported by grants from the Welch Foundation (I-1939), CPRIT (RP170671), National Institutes of Health (R00NS078049, R35GM124693, and R01AG066166), Darrell K Royal Research Fund, TIBIR pilot Grant, the University of Texas Southwestern Medical Center Startup funds and UT Rising Stars to Y.W.; CPRIT (RR160101) to G.L.; Welch Foundation (I-1879), National Institutes of Health (R37CA226771 and R01CA217333) to D.N.; National Institutes of Health (R00CA168746 and R01CA222393), CPRIT (RR140036 and RP190358), Susan G. Komen{\textregistered} Foundation (CCR16376227), Mary Kay Foundation (08-19), and Welch Foundation (I-1903) to W.L. W.L. is a CPRIT Scholar in Cancer Research. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1038/s41467-021-23264-z",
language = "English (US)",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}