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  Lymphocyte-Specific Function of the DNA Plymerase Epsilon Subunit Pole3 Revealed by Neomorphic Alleles

Siamishi, I., Iwanami, N., Clapes, T., Trompouki, E., O'Meara, C. P., & Boehm, T. (2020). Lymphocyte-Specific Function of the DNA Plymerase Epsilon Subunit Pole3 Revealed by Neomorphic Alleles. Cell Reports, 31, 107756. doi:org/10.1016/j.celrep.2020.107756.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0006-A16A-D Version Permalink: http://hdl.handle.net/21.11116/0000-0006-A16B-C
Genre: Journal Article

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2020
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 Creators:
Siamishi, Iliana1, Author
Iwanami, Norimasa1, 2, Author
Clapes, Thomas1, Author
Trompouki, Eirini1, Author              
O'Meara, Connor P.1, Author
Boehm, Thomas1, Author              
Affiliations:
1Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              
2External Organizations, ou_persistent22              

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 Abstract: Immunodeficiencies are typically caused by loss-of-function mutations in lymphocyte-specific genes. Occasionally, mutations in ubiquitous general-purpose factors, including those affecting essential components of the DNA polymerase epsilon (POLE) holoenzyme, have cell-type-specific consequences. POLE3, one of the four components of the POLE holoenzyme, features a histone fold domain and a unique acidic C terminus, making it a particularly attractive candidate mediating cell type-specific activities of POLE. Mice lacking Pole3 survive up to late embryonic stages, indicating that this subunit is dispensable for DNA replication. The phenotypes of viable hypomorphic and neomorphic alleles are surprisingly tissue restricted and reveal a stage-specific function of the histone fold domain of Pole3 during T and B cell development. Gradual introduction of positively charged residues into the acidic C terminus leads to peripheral lymphopenia of increasing severity. Our findings serve as a paradigm to understand the molecular basis of cell-type-specific non-replicative functions of the ubiquitous POLE complex.

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Language(s): eng - English
 Dates: 2020-06-16
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: org/10.1016/j.celrep.2020.107756
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Title: Cell Reports
Source Genre: Journal
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Publ. Info: Maryland Heights, MO : Cell Press
Pages: - Volume / Issue: 31 Sequence Number: - Start / End Page: 107756 Identifier: ISSN: 2211-1247
CoNE: https://pure.mpg.de/cone/journals/resource/2211-1247