Epigenetic shielding: 5-hydroxymethylcytosine and 5-carboxylcytosine modulate UV induction of DNA photoproducts

DSpace/Manakin Repository

Epigenetic shielding: 5-hydroxymethylcytosine and 5-carboxylcytosine modulate UV induction of DNA photoproducts

Citable link to this page

 

 
Title: Epigenetic shielding: 5-hydroxymethylcytosine and 5-carboxylcytosine modulate UV induction of DNA photoproducts
Author: Liu, Jue Judy
Citation: Liu, Jue Judy. 2014. Epigenetic shielding: 5-hydroxymethylcytosine and 5-carboxylcytosine modulate UV induction of DNA photoproducts. Doctoral dissertation, Harvard University.
Full Text & Related Files:
Abstract: Maintaining the balance between dynamic DNA methylation and demethylation is crucial to mammalian development and pathogenesis. In vitro methylation at the C-5 position of cytosine enhances cyclobutane pyrimidine dimer (CPD) formation and promotes transition mutations. While the loss of 5-hydroxymethylcytosine (5hmC) and inactivation of the ten-eleven translocation (TET) family have been implicated in cancers, and repeated exposure to UV radiation is a known risk factor for developing skin cancers, the link between DNA demethylation and UV damage has not yet been illustrated. We report that hydroxylation and carboxylation of 5-methylcytosine mitigate methylation-induced CPD enhancement upon UV irradiation. However, 5hmC also increases UV induction of (6-4) photoproducts. In a melanoma cell model, this duality by 5hmC in modulating the UV response is accentuated through TET2 overexpression. These findings implicate the DNA demethylation intermediates 5-hydroxymethylcytosine (5hmC) and 5-carboxylcytosine (5caC) as selective epigenetic shields against UV induction of DNA photoproducts.
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12274469
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters