Abstract：
:The accumulation of somatic mitochondrial DNA (mtDNA) mutations contributes to the pathogenesis of human disease. Currently, mitochondrial mutations are largely considered results of inaccurate processing of its heavily damaged genome. However, mainly from a lack of methods to monitor mtDNA mutations with sufficient sensitivity and accuracy, a link between mtDNA damage and mutation has not been established. To test the hypothesis that mtDNA-damaging agents induce mtDNA mutations, we exposed MutaTMMouse mice to benzo[a]pyrene (B[a]P) or N-ethyl-N-nitrosourea (ENU), daily for 28 consecutive days, and quantified mtDNA point and deletion mutations in bone marrow and liver using our newly developed Digital Random Mutation Capture (dRMC) and Digital Deletion Detection (3D) assays. Surprisingly, our results demonstrate mutagen treatment did not increase mitochondrial point or deletion mutation frequencies, despite evidence both compounds increase nuclear DNA mutations and demonstrated B[a]P adduct formation in mtDNA. These findings contradict models of mtDNA mutagenesis that assert the elevated rate of mtDNA mutation stems from damage sensitivity and abridged repair capacity. Rather, our results demonstrate induced mtDNA damage does not readily convert into mutation. These findings suggest robust mitochondrial damage responses repress induced mutations after mutagen exposure.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Valente WJ,Ericson NG,Long AS,White PA,Marchetti F,Bielas JHdoi
10.1093/nar/gkw716subject
Has Abstractpub_date
2016-10-14 00:00:00pages
8513-8524issue
18eissn
0305-1048issn
1362-4962pii
gkw716journal_volume
44pub_type
杂志文章abstract：:Kaposi's sarcoma-associated herpesvirus encodes four viral homologues to cellular interferon regulatory factors (IRFs), where the most studied is vIRF-1. Even though vIRF-1 shows sequence homology to the N-terminal DNA-binding domain (DBD) of human IRFs, a specific role for this domain in vIRF-1's function has remaine...
journal_title：Nucleic acids research
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doi：10.1093/nar/gkt082
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journal_title：Nucleic acids research
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doi：10.1093/nar/gky1036
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abstract：:Type III restriction enzymes have been demonstrated to require two unmethylated asymmetric recognition sites oriented head-to-head to elicit double-strand break 25-27 bp downstream of one of the two sites. The proposed DNA cleavage mechanism involves ATP-dependent DNA translocation. The sequence context of the recogni...
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doi：10.1093/nar/gkh899
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pub_type： 杂志文章
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journal_title：Nucleic acids research
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更新日期：2000-01-01 00:00:00
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journal_title：Nucleic acids research
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journal_title：Nucleic acids research
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journal_title：Nucleic acids research
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journal_title：Nucleic acids research
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更新日期：2015-10-15 00:00:00
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journal_title：Nucleic acids research
pub_type： 杂志文章
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更新日期：2002-11-15 00:00:00
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更新日期：1991-12-01 00:00:00
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journal_title：Nucleic acids research
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更新日期：2014-12-01 00:00:00
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journal_title：Nucleic acids research
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更新日期：2008-07-01 00:00:00
