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Site-Specific 5-Formyl Cytosine Mediated DNA-Histone Cross-Links: Synthesis and Polymerase Bypass by Human DNA Polymerase η.
Pujari, Suresh S; Wu, Mingxuan; Thomforde, Jenna; Wang, Zhipeng A; Chao, Christopher; Olson, Noelle M; Erber, Luke; Pomerantz, William C K; Cole, Philip; Tretyakova, Natalia Y.
Afiliação
  • Pujari SS; Department of Medicinal Chemistry, College of Pharmacy, and Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA.
  • Wu M; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
  • Thomforde J; Current address: School of Science, Westlake University, Institute of Natural Sciences, Westlake Institute for Advanced Study, 18 Shilongshan Road, 310024, Hangzhou, Zhejiang Province, China.
  • Wang ZA; Department of Medicinal Chemistry, College of Pharmacy, and Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA.
  • Chao C; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
  • Olson NM; Department of Medicinal Chemistry, College of Pharmacy, and Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA.
  • Erber L; Department of Chemistry, University of Minnesota, Minneapolis, MN, 55455, USA.
  • Pomerantz WCK; Department of Medicinal Chemistry, College of Pharmacy, and Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA.
  • Cole P; Department of Chemistry, University of Minnesota, Minneapolis, MN, 55455, USA.
  • Tretyakova NY; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
Angew Chem Int Ed Engl ; 60(51): 26489-26494, 2021 12 13.
Article em En | MEDLINE | ID: mdl-34634172
ABSTRACT
DNA-protein cross-links (DPCs) between DNA epigenetic mark 5-formylC and lysine residues of histone proteins spontaneously form in human cells. Such conjugates are likely to influence chromatin structure and mediate DNA replication, transcription, and repair, but are challenging to study due to their reversible nature. Here we report the construction of site specific, hydrolytically stable DPCs between 5fdC in DNA and K4 of histone H3 and an investigation of their effects on DNA replication. Our approach employs oxime ligation, allowing for site-specific conjugation of histones to DNA under physiological conditions. Primer extension experiments revealed that histone H3-DNA crosslinks blocked DNA synthesis by hPol η polymerase, but were bypassed following proteolytic processing.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: DNA / Histonas / Citosina / DNA Polimerase Dirigida por DNA Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: DNA / Histonas / Citosina / DNA Polimerase Dirigida por DNA Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article