气候变化领域集成服务门户(CCPortal): PIAS1 modulates striatal transcription, DNA damage repair, and SUMOylation with relevance to Huntington’s disease

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DOI	10.1073/pnas.2021836118
	PIAS1 modulates striatal transcription, DNA damage repair, and SUMOylation with relevance to Huntington’s disease
	Morozko E.L.; Smith-Geater C.; Monteys A.M.; Pradhan S.; Lim R.G.; Langfelder P.; Kachemov M.; Hill A.; Stocksdale J.T.; Cullis P.R.; Wu J.; Ochaba J.; Miramontes R.; Chakraborty A.; Hazra T.K.; Lau A.; St-Cyr S.; Orellana I.; Kopan L.; Wang K.Q.; Yeung S.; Leavitt B.R.; Reidling J.C.; William Yang X.; Steffan J.S.; Davidson B.L.; Sarkar P.S.; Thompson L.M.
发表日期	2021
ISSN	00278424
卷号	118 期号:4
英文摘要	DNA damage repair genes are modifiers of disease onset in Huntington’s disease (HD), but how this process intersects with associated disease pathways remains unclear. Here we evaluated the mechanistic contributions of protein inhibitor of activated STAT-1 (PIAS1) in HD mice and HD patient-derived induced pluripotent stem cells (iPSCs) and find a link between PIAS1 and DNA damage repair pathways. We show that PIAS1 is a component of the transcription-coupled repair complex, that includes the DNA damage end processing enzyme polynucleotide kinase-phosphatase (PNKP), and that PIAS1 is a SUMO E3 ligase for PNKP. Pias1 knockdown (KD) in HD mice had a normalizing effect on HD transcriptional dysregulation associated with synaptic function and disease-associated transcriptional coexpression modules enriched for DNA damage repair mechanisms as did reduction of PIAS1 in HD iPSC-derived neurons. KD also restored mutant HTT-perturbed enzymatic activity of PNKP and modulated genomic integrity of several transcriptionally normalized genes. The findings here now link SUMO modifying machinery to DNA damage repair responses and transcriptional modulation in neurodegenerative disease. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	DNA damage repair; Huntington’s disease; PIAS; PNKP; SUMO
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180891
作者单位	Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, United States; Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697, United States; Raymond G. Perelman Center for Cell and Molecular Therapeutics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, United States; Department of Neurology, University of Texas Medical Branch, Galveston, TX 77555, United States; Institute of Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697, United States; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States; Incisive Genetics Inc., Vancouver, BC V6A 0H9, Canada; NanoMedicines Innovation Network, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Biological Chemistry, University of Californi...
推荐引用方式 GB/T 7714	Morozko E.L.,Smith-Geater C.,Monteys A.M.,等. PIAS1 modulates striatal transcription, DNA damage repair, and SUMOylation with relevance to Huntington’s disease[J],2021,118(4).
APA	Morozko E.L..,Smith-Geater C..,Monteys A.M..,Pradhan S..,Lim R.G..,...&Thompson L.M..(2021).PIAS1 modulates striatal transcription, DNA damage repair, and SUMOylation with relevance to Huntington’s disease.Proceedings of the National Academy of Sciences of the United States of America,118(4).
MLA	Morozko E.L.,et al."PIAS1 modulates striatal transcription, DNA damage repair, and SUMOylation with relevance to Huntington’s disease".Proceedings of the National Academy of Sciences of the United States of America 118.4(2021).