| Title | DNA polymerase-alpha regulates the activation of type I interferons through cytosolic RNA:DNA synthesis |
| Authors | Starokadomskyy, Petro Gemelli, Terry Rios, Jonathan J. Xing, Chao Wang, Richard C. Li, Haiying Pokatayev, Vladislav Dozmorov, Igor Khan, Shaheen Miyata, Naoteru Fraile, Guadalupe Raj, Prithvi Xu, Zhe Xu, Zigang Ma, Lin Lin, Zhimiao Wang, Huijun Yang, Yong Ben-Amitai, Dan Orenstein, Naama Mussaffi, Huda Baselga, Eulalia Tadini, Gianluca Grunebaum, Eyal Sarajlija, Adrijan Krzewski, Konrad Wakeland, Edward K. Yan, Nan de la Morena, Maria Teresa Zinn, Andrew R. Burstein, Ezra |
| Affiliation | Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. Univ Texas SW Med Ctr Dallas, Eugene McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA. Texas Scottish Rite Hosp Children, Sarah M & Charles E Seay Ctr Musculoskeletal Res, Dallas, TX 75219 USA. Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. Univ Texas SW Med Ctr Dallas, Dept Dermatol, Dallas, TX 75390 USA. Univ Texas SW Med Ctr Dallas, Dept Immunol, Dallas, TX 75390 USA. Ramon y Cajal Univ Hosp, Dept Internal Med, Madrid, Spain. Capital Med Univ, Beijing Childrens Hosp, Dept Dermatol, Beijing, Peoples R China. Peking Univ, Hosp 1, Dept Dermatol, Beijing 100871, Peoples R China. Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China. Peking Univ, Acad Adv Interdisciplinary Studies, Beijing 100871, Peoples R China. Schneider Childrens Med Ctr Israel, Unit Pediat Dermatol, Petah Tiqwa, Israel. Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. Schneider Childrens Med Ctr Israel, Genet Unit, Petah Tiqwa, Israel. Schneider Childrens Med Ctr, Pulmonol Inst, Petah Tiqwa, Israel. Hosp Santa Creu & Sant Pau, Dept Dermatol, Barcelona, Spain. Univ Milan, Dept Pathophysiol & Transplantat, Pediat Dermatol Unit, Milan, Italy. Univ Milan, Dept Pathophysiol & Transplantat, Pediat Highly Intens Care Unit, Milan, Italy. IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy. Hosp Sick Children, Dev & Stem Cell Biol Program, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. Univ Toronto, Hosp Sick Children, Div Immunol & Allergy, Toronto, ON M5G 1X8, Canada. Mother & Child Hlth Care Inst Serbia, Belgrade, Serbia. Univ Belgrade, Sch Med, Belgrade, Serbia. NIAID, Immunogenet Lab, Receptor Cell Biol Sect, NIH, Rockville, MD USA. Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA. Childrens Hlth, Dallas, TX USA. Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA. Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. Zinn, AR (reprint author), Univ Texas SW Med Ctr Dallas, Eugene McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA. Burstein, E (reprint author), Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA. |
| Keywords | RETICULATE PIGMENTARY DISORDER NF-KAPPA-B SYSTEMIC MANIFESTATIONS CUTANEOUS AMYLOIDOSIS DEFICIENCY DISEASE HUMANS FAMILY ENCEPHALITIS REPLICATION |
| Issue Date | 2016 |
| Publisher | NATURE IMMUNOLOGY |
| Citation | NATURE IMMUNOLOGY.2016,17,(5),495-+. |
| Abstract | Aberrant nucleic acids generated during viral replication are the main trigger for antiviral immunity, and mutations that disrupt nucleic acid metabolism can lead to autoinflammatory disorders. Here we investigated the etiology of X-linked reticulate pigmentary disorder (XLPDR), a primary immunodeficiency with autoinflammatory features. We discovered that XLPDR is caused by an intronic mutation that disrupts the expression of POLA1, which encodes the catalytic subunit of DNA polymerase-alpha. Unexpectedly, POLA1 deficiency resulted in increased production of type I interferons. This enzyme is necessary for the synthesis of RNA: DNA primers during DNA replication and, strikingly, we found that POLA1 is also required for the synthesis of cytosolic RNA: DNA, which directly modulates interferon activation. Together this work identifies POLA1 as a critical regulator of the type I interferon response. |
| URI | http://hdl.handle.net/20.500.11897/434356 |
| ISSN | 1529-2908 |
| DOI | 10.1038/ni.3409 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 第一医院 前沿交叉学科研究院 |
