1. A nuclease that mediates cell death induced by DNA damage and poly(ADP-ribose) polymerase-1
- Author
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Jun Seop Jeong, Stewart Neifert, Jiang Qian, Ted M. Dawson, Bong Woo Kim, Kalyani Nambiar, Guo Li Ming, Yingfei Wang, Lei Bao, Maged M. Harraz, Hyejin Park, Hongjun Song, Shaida A. Andrabi, Zhi Xie, Heng Zhu, Tae In Kam, Calvin Chang, Jennifer E. Wang, Seth Blackshaw, Valina L. Dawson, Rong Chen, Ran An, Stephen M. Eacker, and George K.E. Umanah
- Subjects
0301 basic medicine ,Programmed cell death ,DNA damage ,Poly ADP ribose polymerase ,Active Transport, Cell Nucleus ,Poly (ADP-Ribose) Polymerase-1 ,DNA, Single-Stranded ,Glutamic Acid ,Apoptosis ,DNA Fragmentation ,Biology ,Mice ,03 medical and health sciences ,Endonuclease ,Catalytic Domain ,Animals ,Humans ,Amino Acid Sequence ,DNA Cleavage ,Macrophage Migration-Inhibitory Factors ,Cell Nucleus ,Mice, Knockout ,Neurons ,Deoxyribonucleases ,Multidisciplinary ,Base Sequence ,Apoptosis Inducing Factor ,Molecular biology ,Chromatin ,Mitochondria ,Intramolecular Oxidoreductases ,Stroke ,Oxidative Stress ,030104 developmental biology ,Mutation ,biology.protein ,Nucleic Acid Conformation ,DNA fragmentation ,Macrophage migration inhibitory factor ,DNA Damage ,HeLa Cells - 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
- Published
- 2016