Iron is an essential redox element that functions as a cofactor in many metabolic pathways. Critical enzymes in DNA metabolism, including multiple DNA repair enzymes (helicases, nucleases, glycosylases, demethylases) and ribonucleotide reductase, use iron as an indispensable cofactor to function. Recent striking results have revealed that the catalytic subunit of DNA polymerases also contains conserved cysteine-rich motifs that bind iron-sulfur (Fe/S) clusters that are essential for the formation of stable and active complexes. In line with this, mitochondrial and cytoplasmic defects in Fe/S cluster biogenesis and insertion into the nuclear iron-requiring enzymes involved in DNA synthesis and repair lead to DNA damage and genome instability. Recent studies have shown that yeast cells possess multi-layered mechanisms that regulate the ribonucleotide reductase function in response to fluctuations in iron bioavailability to maintain optimal deoxyribonucleotide concentrations. Finally, a fascinating DNA charge transport model indicates how the redox active Fe/S centers present in DNA repair machinery components are critical for detecting and repairing DNA mismatches along the genome by long-range charge transfers through double-stranded DNA. These unexpected connections between iron and DNA replication and repair have to be considered to properly understand cancer, aging and other DNA-related diseases.

中文翻译：

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铁在DNA合成和修复中的元素作用

铁是必不可少的氧化还原元素，在许多代谢途径中起辅助因子的作用。DNA代谢中的关键酶，包括多种DNA修复酶（核酸酶，核酸酶，糖基化酶，脱甲基酶）和核糖核苷酸还原酶，都将铁用作功能必需的辅酶。最近的惊人结果表明，DNA聚合酶的催化亚基还包含保守的富含半胱氨酸的基序，这些基序与铁硫（Fe / S）簇结合，这对形成稳定和活性的复合物至关重要。与此相一致，Fe / S中的线粒体和细胞质缺陷使生物发生簇生并插入涉及DNA合成和修复的需要核铁的酶中，从而导致DNA损伤和基因组不稳定。最近的研究表明，酵母细胞具有多层机制，可响应铁生物利用度的波动来调节核糖核苷酸还原酶的功能，以维持最佳的脱氧核糖核苷酸浓度。最后，一个令人着迷的DNA电荷传输模型表明，DNA修复机制组件中存在的氧化还原活性Fe / S中心对于通过双链DNA进行长距离电荷转移来检测和修复沿着基因组的DNA不匹配至关重要。为了正确理解癌症，衰老和其他与DNA有关的疾病，必须考虑铁与DNA复制和修复之间的这些意想不到的联系。令人着迷的DNA电荷传输模型表明，DNA修复机制组件中存在的氧化还原活性Fe / S中心对于通过双链DNA进行长距离电荷转移来检测和修复沿基因组的DNA错配至关重要。为了正确理解癌症，衰老和其他与DNA有关的疾病，必须考虑铁与DNA复制和修复之间的这些意想不到的联系。令人着迷的DNA电荷传输模型表明，DNA修复机制组件中存在的氧化还原活性Fe / S中心对于通过双链DNA进行长距离电荷转移来检测和修复沿基因组的DNA错配至关重要。为了正确理解癌症，衰老和其他与DNA有关的疾病，必须考虑铁与DNA复制和修复之间的这些意想不到的联系。