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

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

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dc.contributor.advisor Fisher, David E.
dc.contributor.author Liu, Jue Judy
dc.date.accessioned 2014-06-06T19:52:41Z
dash.embargo.terms 2014-12-04 en_US
dash.embargo.terms 2014-12-04
dc.date.issued 2014-06-06
dc.date.submitted 2014
dc.identifier.citation Liu, Jue Judy. 2014. Epigenetic shielding: 5-hydroxymethylcytosine and 5-carboxylcytosine modulate UV induction of DNA photoproducts. Doctoral dissertation, Harvard University. en_US
dc.identifier.other http://dissertations.umi.com/gsas.harvard:11602 en
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:12274469
dc.description.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. en_US
dc.language.iso en_US en_US
dash.license LAA
dc.subject Biochemistry en_US
dc.title Epigenetic shielding: 5-hydroxymethylcytosine and 5-carboxylcytosine modulate UV induction of DNA photoproducts en_US
dc.type Thesis or Dissertation en_US
dash.depositing.author Liu, Jue Judy
dc.date.available 2014-12-04T08:30:53Z
thesis.degree.date 2014 en_US
thesis.degree.discipline Biology: Medical Sciences, Division of en_US
thesis.degree.grantor Harvard University en_US
thesis.degree.level doctoral en_US
thesis.degree.name Ph.D. en_US
dc.contributor.committeeMember Frank, David en_US
dc.contributor.committeeMember Wu, Xu en_US
dc.contributor.committeeMember Dedon, Peter en_US

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