5-HYDROXYPYRIMIDINE DEOXYNUCLEOSIDE TRIPHOSPHATES ARE MORE EFFICIENTLY INCORPORATED INTO DNA BY EXONUCLEASE-FREE KLENOW FRAGMENT THAN 8-OXOPURINE DEOXYNUCLEOSIDE TRIPHOSPHATES
5-HYDROXYPYRIMIDINE DEOXYNUCLEOSIDE TRIPHOSPHATES ARE MORE EFFICIENTLY INCORPORATED INTO DNA BY EXONUCLEASE-FREE KLENOW FRAGMENT THAN 8-OXOPURINE DEOXYNUCLEOSIDE TRIPHOSPHATES
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DOI：
10.1093/nar/22.19.3930
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发表时间：
1994-09-25
影响因子：
14.9
通讯作者：
WALLACE, SS
中科院分区：
文献类型：
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作者：
PURMAL, AA;KOW, YW;WALLACE, SS
最近对8-氧代脱氧鸟苷三磷酸（8-oxodGTP）的研究表明，将前体库中的氧化核苷酸掺入DNA可能具有有害作用。在这里，我们表明，5-羟基脱氧胞嘧啶三磷酸（5-OHdCTP）和5-羟基脱氧尿苷三磷酸（5-OHdUTP）是更有效的底物比8-oxodGTP的大肠杆菌DNA聚合酶I Klenow片段缺乏校对活性，而8-oxodATP（8-oxodATP）是效率低得多。此外，与8-oxodGTP一样，5-OHdCTP可以与DNA中的dA错配，但效率较低。由于5-羟基嘧啶存在于正常和氧化的细胞DNA中，其量与8-氧代嘌呤相似，因此这些数据表明可能存在将其从DNA前体池中去除的酶促机制。
Recent studies with 8-oxodeoxyguanosine triphosphate (8-oxodGTP) have suggested that incorporation of oxidized nucleotides from the precursor pool into DNA may have deleterious effects. Here we show that 5-hydroxydeoxycytosine triphosphate (5-OHdCTP) and 5-hydroxydeoxyuridine triphosphate (5-OHdUTP) are more efficient substrates than 8-oxodGTP for Escherichia coli DNA polymerase I Klenow fragment lacking proofreading activity, while 8-oxodeoxyadenosine triphosphate (8-oxodATP) is much less efficient. Furthermore, like 8-oxodGTP, 5-OHdCTP can mispair with dA in DNA but with lower efficiency. Since the 5-hydroxypyrimidines are present in normal and oxidized cellular DNA in amounts similar to the 8-oxopurines, these data suggest that enzymatic mechanisms might exist for removing them from the DNA precursor pools.