Fold-back structures at the distal end influence DNA slippage at the proximal end during mononucleotide repeat expansions
Fold-back structures at the distal end influence DNA slippage at the proximal end during mononucleotide repeat expansions
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DOI：
10.1093/nar/27.19.3851
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发表时间：
1999-10-01
影响因子：
14.9
通讯作者：
Rao, BJ
中科院分区：
文献类型：
--
作者：
Karthikeyan, G;Chary, KVR;Rao, BJ
研究了DNA聚合酶跨A、C、G和T重复序列(30个碱基)的Klenow片段在DNA合成过程中的聚合酶滑移。在几分钟内，只包含重复序列(30bp)的双链急剧扩大到数百个碱基对的长度。在重复的双链中，当一条链被扩展时，与当浴链被扩展时的速率进行比较，提出了一种迁移发夹环的模型，在后一种情况下，这些发夹环结合成一个双链。此外，滑移(在近端或3‘端)受到同一链的5’端(远端)的正负效应的影响。生长的T和G链在远端产生T，A：T和G-G：C基序折叠结构，阻止近端的滑动。另一方面，在用过量的互补模板退火时，在远端生长的尾巴会使近端的滑移增加数倍。
Polymerase slippage during DNA synthesis by the Klenow fragment of DNA polymerase across A, C, G and T repeats (30 bases) has been studied. Within minutes, duplexes that contain only repeats (30 bp) expand dramatically to several hundred base pairs long. Rate comparisons in a repeat duplex when one strand was expanded as against that when bath strands were expanded suggest a model of migrating hairpin loops which in the latter case coalesce into a duplex. Moreover, slippage (at the proximal or 3'-end) is subject to positive and negative effects from the 5'-end (distal) of the same strand. Growing T and G strands generate T,A:T and G-G:C motif fold-back structures at the distal end that hamper slippage at the proximal end. On the other hand, growing tails at the distal end upon annealing with excess complementary template accentuates proximal slippage several-fold.