MIF is a 3’ flap nuclease that facilitates DNA replication and promotes tumor growth

Yijie Wang, Yan Chen, Chenliang Wang, Mingming Yang, Yanan Wang, Lei Bao, Jennifer E. Wang, BongWoo Kim, Kara Y. Chan, Weizhi Xu, Emanuela Capota, Janice Ortega, Deepak Nijhawan, Guo-Min Li, Weibo Luo and Yingfei Wang ()
Additional contact information
Yijie Wang: UT Southwestern Medical Center
Yan Chen: UT Southwestern Medical Center
Chenliang Wang: UT Southwestern Medical Center
Mingming Yang: UT Southwestern Medical Center
Yanan Wang: UT Southwestern Medical Center
Lei Bao: UT Southwestern Medical Center
Jennifer E. Wang: UT Southwestern Medical Center
BongWoo Kim: UT Southwestern Medical Center
Kara Y. Chan: UT Southwestern Medical Center
Weizhi Xu: UT Southwestern Medical Center
Emanuela Capota: UT Southwestern Medical Center
Janice Ortega: UT Southwestern Medical Center
Deepak Nijhawan: UT Southwestern Medical Center
Guo-Min Li: UT Southwestern Medical Center
Weibo Luo: UT Southwestern Medical Center
Yingfei Wang: UT Southwestern Medical Center

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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’ 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’ nuclease, excises flaps at the immediate 3’ end during DNA synthesis and favors cancer cells evading replication stress-induced threat for their growth.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-23264-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23264-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-23264-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().