Uracil DNA N-glycosylase promotes assembly of human centromere protein A.
Uracil is removed from DNA by the conserved enzyme uracil DNA N-glycosylase (UNG). Previously, we observed that inhibiting UNG in Xenopus egg extracts blocked assembly of CENP-A, a histone H3 variant. CENP-A is an essential protein in all species, since it is required for chromosome segregation duri...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-03-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3047565?pdf=render |
| _version_ | 1819181703638286336 |
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| author | Samantha G Zeitlin Brian R Chapados Norman M Baker Caroline Tai Geir Slupphaug Jean Y J Wang |
| author_facet | Samantha G Zeitlin Brian R Chapados Norman M Baker Caroline Tai Geir Slupphaug Jean Y J Wang |
| author_sort | Samantha G Zeitlin |
| collection | DOAJ |
| description | Uracil is removed from DNA by the conserved enzyme uracil DNA N-glycosylase (UNG). Previously, we observed that inhibiting UNG in Xenopus egg extracts blocked assembly of CENP-A, a histone H3 variant. CENP-A is an essential protein in all species, since it is required for chromosome segregation during mitosis. Thus, the implication of UNG in CENP-A assembly implies that UNG would also be essential, but UNG mutants lacking catalytic activity are viable in all species. In this paper, we present evidence that UNG2 colocalizes with CENP-A and H2AX phosphorylation at centromeres in normally cycling cells. Reduction of UNG2 in human cells blocks CENP-A assembly, and results in reduced cell proliferation, associated with increased frequencies of mitotic abnormalities and rapid cell death. Overexpression of UNG2 induces high levels of CENP-A assembly in human cells. Using a multiphoton laser approach, we demonstrate that UNG2 is rapidly recruited to sites of DNA damage. Taken together, our data are consistent with a model in which the N-terminus of UNG2 interacts with the active site of the enzyme and with chromatin. |
| first_indexed | 2024-12-22T22:34:27Z |
| format | Article |
| id | doaj.art-daa6d77585eb4b38b51f181627e19706 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T22:34:27Z |
| publishDate | 2011-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-daa6d77585eb4b38b51f181627e197062022-12-21T18:10:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-03-0163e1715110.1371/journal.pone.0017151Uracil DNA N-glycosylase promotes assembly of human centromere protein A.Samantha G ZeitlinBrian R ChapadosNorman M BakerCaroline TaiGeir SlupphaugJean Y J WangUracil is removed from DNA by the conserved enzyme uracil DNA N-glycosylase (UNG). Previously, we observed that inhibiting UNG in Xenopus egg extracts blocked assembly of CENP-A, a histone H3 variant. CENP-A is an essential protein in all species, since it is required for chromosome segregation during mitosis. Thus, the implication of UNG in CENP-A assembly implies that UNG would also be essential, but UNG mutants lacking catalytic activity are viable in all species. In this paper, we present evidence that UNG2 colocalizes with CENP-A and H2AX phosphorylation at centromeres in normally cycling cells. Reduction of UNG2 in human cells blocks CENP-A assembly, and results in reduced cell proliferation, associated with increased frequencies of mitotic abnormalities and rapid cell death. Overexpression of UNG2 induces high levels of CENP-A assembly in human cells. Using a multiphoton laser approach, we demonstrate that UNG2 is rapidly recruited to sites of DNA damage. Taken together, our data are consistent with a model in which the N-terminus of UNG2 interacts with the active site of the enzyme and with chromatin.http://europepmc.org/articles/PMC3047565?pdf=render |
| spellingShingle | Samantha G Zeitlin Brian R Chapados Norman M Baker Caroline Tai Geir Slupphaug Jean Y J Wang Uracil DNA N-glycosylase promotes assembly of human centromere protein A. PLoS ONE |
| title | Uracil DNA N-glycosylase promotes assembly of human centromere protein A. |
| title_full | Uracil DNA N-glycosylase promotes assembly of human centromere protein A. |
| title_fullStr | Uracil DNA N-glycosylase promotes assembly of human centromere protein A. |
| title_full_unstemmed | Uracil DNA N-glycosylase promotes assembly of human centromere protein A. |
| title_short | Uracil DNA N-glycosylase promotes assembly of human centromere protein A. |
| title_sort | uracil dna n glycosylase promotes assembly of human centromere protein a |
| url | http://europepmc.org/articles/PMC3047565?pdf=render |
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