RPA and PCNA suppress formation of large deletion errors by yeast DNA polymerase delta.
RPA and PCNA suppress formation of large deletion errors by yeast DNA polymerase delta.
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DOI：
10.1093/nar/gkl403
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发表时间：
2006
影响因子：
14.9
通讯作者：
Kunkel TA
中科院分区：
文献类型：
--
作者：
Fortune JM;Stith CM;Kissling GE;Burgers PM;Kunkel TA
在核复制以及几种修复类型中履行其生物合成作用时，DNA聚合酶δ（pol δ）受到复制蛋白A（RPA，单链DNA结合蛋白复合物）以及持续性夹钳增殖细胞核抗原（PCNA）的协助。在此我们报道了这些辅助蛋白对酵母pol δ在体外DNA合成保真度的影响。我们表明，当RPA和PCNA包含在含有pol δ的反应中时，单碱基错误的比率与pol δ单独产生的比率相似，这表明pol δ本身是迄今为止单碱基错误保真度的主要决定因素。然而，在直接重复序列之间缺失多个核苷酸的比率在有RPA或PCNA存在时降低了约10倍，并且当两种蛋白都存在时降低了≥90倍。我们认为PCNA和RPA通过防止重复序列处的引物末端散开和/或重新定位并与下游重复序列退火来抑制大片段缺失错误。PCNA和RPA对缺失的强烈抑制表明它们可能有助于稳定维持含有大量重复序列的真核生物基因组所需的高复制保真度。
In fulfilling its biosynthetic roles in nuclear replication and in several types of repair, DNA polymerase δ (pol δ) is assisted by replication protein A (RPA), the single-stranded DNA-binding protein complex, and by the processivity clamp proliferating cell nuclear antigen (PCNA). Here we report the effects of these accessory proteins on the fidelity of DNA synthesis in vitro by yeast pol δ. We show that when RPA and PCNA are included in reactions containing pol δ, rates for single base errors are similar to those generated by pol δ alone, indicating that pol δ itself is by far the prime determinant of fidelity for single base errors. However, the rate of deleting multiple nucleotides between directly repeated sequences is reduced by ∼10-fold in the presence of either RPA or PCNA, and by ≥90-fold when both proteins are present. We suggest that PCNA and RPA suppress large deletion errors by preventing the primer terminus at a repeat from fraying and/or from relocating and annealing to a downstream repeat. Strong suppression of deletions by PCNA and RPA suggests that they may contribute to the high replication fidelity needed to stably maintain eukaryotic genomes that contain abundant repetitive sequences.
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DOI：
10.1101/sqb.2000.65.81
发表时间：
2000-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
Bebenek, K;Kunkel, TA
通讯作者：
Kunkel, TA
影响因子：
4.8
作者：
Bloom, LB;Chen, XL;Goodman, MF
通讯作者：
Goodman, MF
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
DOI：
10.1073/pnas.91.15.6830
发表时间：
1994-07-19
影响因子：
11.1
作者：
KUNKEL, TA;PATEL, SS;JOHNSON, KA
通讯作者：
JOHNSON, KA
影响因子：
4.8
作者：
Mo, JY;Schaaper, RM
通讯作者：
Schaaper, RM