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1.
Sci Rep ; 4: 5220, 2014 Jun 09.
Article in English | MEDLINE | ID: mdl-24910358

ABSTRACT

The genetic information encoded in genomes must be faithfully replicated and transmitted to daughter cells. The recent discovery of consecutive DNA conversions by TET family proteins of 5-methylcytosine into 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine (5caC) suggests these modified cytosines act as DNA lesions, which could threaten genome integrity. Here, we have shown that although 5caC pairs with guanine during DNA replication in vitro, G·5caC pairs stimulated DNA polymerase exonuclease activity and were recognized by the mismatch repair (MMR) proteins. Knockdown of thymine DNA glycosylase increased 5caC in genome, affected cell proliferation via MMR, indicating MMR is a novel reader for 5caC. These results suggest the epigenetic modification products of 5caC behave as DNA lesions.


Subject(s)
Base Pairing/genetics , Cytosine/analogs & derivatives , DNA Mismatch Repair/genetics , DNA Replication/genetics , Guanine/metabolism , 5-Methylcytosine/metabolism , Cell Proliferation/genetics , Cytosine/metabolism , DNA/genetics , Epigenesis, Genetic/genetics , Humans , Thymine DNA Glycosylase/metabolism
2.
J Virol ; 87(7): 4086-90, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23325683

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) infection of most human cells is dependent on cyclophilin A (CypA); however, the opposite phenomenon, known as CypA-dependent inhibition, is also observed in the combination of some capsid (CA) mutations and cell lines. Here, we identified a CA N121K mutant whose infection of 293T, Jurkat, and HeLa cells was impaired by CypA. The N121K mutant could be a useful tool for analyzing the mechanisms underlying CypA-dependent restriction.


Subject(s)
Capsid Proteins/genetics , Cyclophilin A/metabolism , HIV Infections/metabolism , HIV-1/genetics , Virus Replication/physiology , Enzyme-Linked Immunosorbent Assay , HEK293 Cells , HIV Core Protein p24/genetics , HeLa Cells , Humans , Jurkat Cells , Luciferases , Mutation, Missense/genetics , Virus Replication/genetics
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