MUTATIONS, DUPLICATION, AND DELETION OF RECOMBINED SWITCH REGIONS SUGGEST A ROLE FOR DNA-REPLICATION IN THE IMMUNOGLOBULIN HEAVY-CHAIN SWITCH

MUTATIONS, DUPLICATION, AND DELETION OF RECOMBINED SWITCH REGIONS SUGGEST A ROLE FOR DNA-REPLICATION IN THE IMMUNOGLOBULIN HEAVY-CHAIN SWITCH
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DOI:
10.1128/mcb.9.5.1850
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发表时间:
1989-05-01
影响因子:
5.3
通讯作者:
STAVNEZER, J
STAVNEZER, J
中科院分区:
生物学2区
文献类型:
--
作者:
DUNNICK, W;WILSON, M;STAVNEZER, J

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从免疫球蛋白M (IgM)表达到IgA表达的重链转换是由称为开关区的DNA片段之间的重组事件介导的。开关区位于.mu上游2到6千碱基处。和.alpha。恒定区域编码段。转换重组到IgA表达会产生重组的。mu.-。alpha。表示的。alpha上游的开关区域。恒定区基因。我们已经对淋巴瘤细胞系I.29的开关重组产物进行了表征。两组分子克隆代表简单.mu的预期产物。.alpha。开关。第三组分子克隆的5个成员在两个。mu中具有相同的重组位点。还有。这意味着这5个分子克隆是由单个开关重组事件产生的。令人惊讶的是,这5个克隆属于两组序列,它们因几个点突变和小的缺失而彼此不同。在这5个分子克隆中也发现了开关区序列的重复。对这些数据的一种解释是,开关重组涉及DNA合成,导致核苷酸取代、小缺失和重复。
The heavy-chain switch from immunoglobulin M (IgM) expression to IgA expression is mediated by a recombination event between segments of DNA called switch regions. The switch regions lie two to six kilobases upstream of the .mu. and .alpha. constant region coding segments. Switch recombination to IgA expression results in a recombinant .mu.-.alpha. switch region upstream of the expressed .alpha. constant region gene. We have characterized the products of switch recombination by a lymphoma cell line, I.29. Two sets of molecular clones represent the exprected products of simple .mu. to .alpha. switches. Five members of a third set of molecular clones share the same recombination site in both the .mu. and the .alpha. switch regions, implying that the five molecular clones were derived from a single switch recombination event. Surpisingly, the five clones fall into two sets of sequences, which differ from each other by several point mutations and small deletions. Duplication of switch region sequences are also found in these five molecular clones. An explanation for these data is that switch recombination involves DNA synthesis, which results in nucleotide substitutions, small deletions, and duplications.