Disease relevance of C02674

• Mutagenic effects of 2-deoxyribonolactone in Escherichia coli. An abasic lesion that disobeys the A-rule [1].
• DNA plasmids containing a specifically located dL downstream of the T3, T7 promoter or the Adenovirus major late promoter were constructed and used for in vitro transcription with purified proteins [2].
• To assess whether dL might be subject to TCR, we have studied the behavior of bacteriophage T3 and T7 RNA polymerases (T3RNAP, T7RNAP) and of mammalian RNA polymerase II (RNAPII) when they encounter a dL lesion or its "caged" precursor located either in the transcribed or in the nontranscribed strand of template DNA [2].

High impact information on C02674

• Long-patch base excision DNA repair of 2-deoxyribonolactone prevents the formation of DNA-protein cross-links with DNA polymerase beta [3].
• Covalent trapping of human DNA polymerase beta by the oxidative DNA lesion 2-deoxyribonolactone [4].
• Chemistry of the 2-deoxyribonolactone lesion in oligonucleotides: cleavage kinetics and products analysis [5].
• On photolysis of deoxycytidine at acidic pH, 2-deoxyribonolactone was produced with 74.2% isolated yield [6].
• Endonuclease IV incision efficiency of 2-deoxyribonolactone or C4-AP was independent of whether the lesion was opposite dA or dG [7].

Biological context of C02674

• 2-Deoxyribonolactone (dL) is a C1'-oxidized abasic site implicated in DNA strand breakage, mutagenesis, and formation of covalent DNA-protein cross-links (DPCs) with repair enzymes such as DNA polymerase beta (polbeta) [3].
• [reaction: see text] An efficient method for the site-specific generation of 2-deoxyribonolactone oxidative DNA damage lesions from a "photocaged" nucleoside analogue was developed [8].
• This raises the possibility that additional repair pathways might be required to eliminate dL from the genome [2].
• Incubation of deoxyribonolactone-containing DNA under simulated physiological conditions gave rise to DNA fragmentation by two consecutive elimination reactions [9].

Associations of C02674 with other chemical compounds

• The 2-deoxyribonolactone lesion produced in DNA by neocarzinostatin and other damaging agents forms cross-links with the base-excision repair enzyme endonuclease III [10].

Gene context of C02674

• Furthermore, RNAPII complexes arrested at dL were subject to the transcript cleavage reaction mediated by elongation factor TFIIS, indicating that these complexes were stable [2].
• In the case of DNA polymerase beta, the reaction is potentiated by incision of dL by Ape1, the major mammalian AP endonuclease [11].
• 2-Deoxyribonolactone is known to cross-link to endonuclease III (Hashimoto, M. (2001) J. Am. Chem. Soc. 123, 3161.). However, the C4-AP lesion is efficiently excised by endonuclease III [7].
• A dL in the nontranscribed strand did not block either polymerase [2].
• Recent work indicates that dL is processed efficiently by Ape1, but that short-patch BER is derailed by the formation of stable covalent crosslinks between Ape1-incised dL and Polbeta [12].

References