Formaldehyde-induced mutagenesis in Saccharomyces cerevisiae: molecular properties and the roles of repair and bypass systems.
Formaldehyde-induced mutagenesis in Saccharomyces cerevisiae: molecular properties and the roles of repair and bypass systems.
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DOI：
10.1016/j.mrfmmm.2011.12.004
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发表时间：
2012-03-01
影响因子：
2.3
通讯作者：
Jinks-Robertson, Sue
中科院分区：
文献类型：
--
作者：
Grogan, Dennis;Jinks-Robertson, Sue
关键词：
尽管DNA-蛋白质交联（DPC）对基因组稳定性构成了重大威胁，但它们仍然是一类知之甚少的DNA损伤。为了从分子角度定义DPC对真核细胞的遗传影响，我们使用灵敏的酿酒酵母移码检测试验来分析甲醛（HCHO）的突变及其对核苷酸切除修复（NER）和跨损伤DNA合成（TLS）的反应。短暂暴露于HCHO对NER缺陷型rad 14菌株具有致突变性，但对相应的RAD 14菌株没有致突变性，对缺乏Pol β和Polη TLS聚合酶的rad 14菌株也没有致突变性。这证实了HCHO产生的DNA损伤可以触发易错TLS，并且是NER途径的底物。测序结果显示，HCHO诱导的单碱基对插入主要发生在一个热点，这些插入也是复杂的，改变了附近的一个额外的碱基对。大多数HCHO诱导的突变需要Pol λ和Polη，这提供了在绕过体内形成的DNA损伤期间这两种TLS聚合酶之间的协同性的突出例子。该系统检测到的HCHO诱导的和自发的复合物+1插入的类似分子性质表明，在正常代谢过程中体内形成的DPC可能对NER缺陷细胞中自发突变的谱贡献特征性事件。
Although DNA-protein cross-links (DPCs) pose a significant threat to genome stability, they remain a poorly understood class of DNA lesions. To define genetic impacts of DPCs on eukaryotic cells in molecular terms, we used a sensitive Saccharomyces cerevisiae frameshift-detection assay to analyze mutagenesis by formaldehyde (HCHO), and its response to nucleotide excision repair (NER) and translesion DNA synthesis (TLS). Brief exposure to HCHO was mutagenic for NER-defective rad14 strains but not for a corresponding RAD14 strain, nor for a rad14 strain lacking both Polζ and Polη TLS polymerases. This confirmed that HCHO-generated DNA lesions can trigger error-prone TLS and are substrates for the NER pathway. Sequencing revealed that HCHO-induced single-base-pair insertions occurred primarily at one hotspot; most of these insertions were also complex, changing an additional base-pair nearby. Most of the HCHO-induced mutations required both Polζ and Polη, providing a striking example of cooperativity between these two TLS polymerases during bypass of a DNA lesion formed in vivo. The similar molecular properties of HCHO-induced and spontaneous complex +1 insertions detected by this system suggest that DPCs which form in vivo during normal metabolism may contribute characteristic events to the spectra of spontaneous mutations in NER-deficient cells.
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DOI：
10.1073/pnas.0600538103
发表时间：
2006-03-14
影响因子：
11.1
作者：
Reardon, JT;Sancar, A
通讯作者：
Sancar, A
DOI：
10.1016/0165-7992(92)90145-8
发表时间：
1992-10-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
KUYKENDALL, JR;BOGDANFFY, MS
通讯作者：
BOGDANFFY, MS
DOI：
10.1073/pnas.0812715106
发表时间：
2009-04-07
影响因子：
11.1
作者：
Lehner, Kevin;Jinks-Robertson, Sue
通讯作者：
Jinks-Robertson, Sue
影响因子：
3.8
作者：
Kim, Nayun;Abdulovic, Amy L.;Jinks-Robertson, Sue
通讯作者：
Jinks-Robertson, Sue
影响因子：
11.2
作者：
Kuo, H. Kenny;Griffith, Jack D.;Kreuzer, Kenneth N.
通讯作者：
Kreuzer, Kenneth N.