IDENTIFICATION AND QUANTITATION OF THE LESION ACCOMPANYING BASE RELEASE IN BLEOMYCIN-MEDIATED DNA-DEGRADATION

IDENTIFICATION AND QUANTITATION OF THE LESION ACCOMPANYING BASE RELEASE IN BLEOMYCIN-MEDIATED DNA-DEGRADATION
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DOI:
10.1021/ja00164a049
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发表时间:
1990-04-11
影响因子:
15
通讯作者:
KOZARICH, JW
KOZARICH, JW
中科院分区:
化学1区
文献类型:
--
作者:
RABOW, LE;STUBBE, J;KOZARICH, JW

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博来霉素、Fe2+ 和限制性 O2 或博来霉素、Fe3+ 和 H2O2 与 DNA 的相互作用会导致游离核酸碱基的产生和氧化损伤的糖损伤,该损伤在用碱处理后会发生链断裂。六聚体 d(CGCGCG) 已用于开发一种方案,以确定该损伤作为 2''-脱氧-4''-戊糖部分的身份,并确定其相对于游离核酸​​碱基的化学计量生产。所开发的方案已扩展到多种异质 DNA,并获得相似的结果。博莱霉素介导的 DNA 降解中碱基释放的主要途径是糖部分的 C-4'' 碳发生化学反应的结果。
Interaction of bleomycin, Fe2+, and limiting O2 or bleomycin, Fe3+, and H2O2 with DNA results in the production of free nucleic acid base and an oxidatively damaged sugar lesion that undergoes strand scission subsequent to treatment with alkali. The hexamer d(CGCGCG) has been utilized to develop a protocol to establish the identity of this lesion as a 2''-deoxy-4''-pentulose moiety and to establish its stoichiometric production with respect to free nucleic acid base. The protocol developed has been extended to a variety of hetergeneous DNAs with similar results. The predominant pathway for base release in bleomycin-mediated DNA degradation is the result of chemistry at the C-4'' carbon of the sugar moiety.