A nuclease that mediates cell death induced by DNA damage and poly(ADP-ribose) polymerase-1

Author:

Wang Yingfei1234,An Ran125,Umanah George K.12,Park Hyejin126,Nambiar Kalyani12,Eacker Stephen M.126,Kim BongWoo3,Bao Lei3,Harraz Maged M.127,Chang Calvin1,Chen Rong12,Wang Jennifer E.3,Kam Tae-In126,Jeong Jun Seop89,Xie Zhi10,Neifert Stewart126,Qian Jiang10,Andrabi Shaida A.12,Blackshaw Seth7910,Zhu Heng89,Song Hongjun127,Ming Guo-li127,Dawson Valina L.126711,Dawson Ted M.12678

Affiliation:

1. Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

2. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

3. Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

4. Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

5. Department of Neurology of Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.

6. Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685, USA.

7. Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

8. Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

9. Center for High-Throughput Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

10. Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

11. Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

DNA damage-activated nuclease identified Cells that experience stresses and accumulate excessive damage to DNA undergo cell death mediated by a nuclear enzyme known as PARP-1. During this process, apoptosis-inducing factor (AIF) translocates to the nucleus and activates one or more nucleases to cleave DNA. Wang et al. found that macrophage migration inhibitory factor (MIF) is an AIF-associated endonuclease that contributes to PARP-1-induced DNA fragmentation (see the Perspective by Jonas). In mouse neurons in culture, loss of MIF protected neurons from cell death caused by excessive stimulation. Targeting MIF could thus provide a therapeutic strategy against diseases in which PARP-1 activation is excessive. Science , this issue p. 82 ; see also p. 36

Funder

American Heart Association (AHA) National Scientist Development

University of Texas Southwestern Medical Center Department of Pathology Startup

UT Rising Stars

National Institute on Drug Abuse

NIH

National Institute of Neurological Disorders and Stroke

Neurodegenerative Diseases

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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