Intrachromosomal mitotic nonallelic homologous recombination is the major molecular mechanism underlying type‐2 NF1 deletions
Intrachromosomal mitotic nonallelic homologous recombination is the major molecular mechanism underlying type‐2 NF1 deletions
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染色体内有丝分裂非等位同源重组是 2 型 NF1 缺失的主要分子机制
DOI：
10.1002/humu.21340
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发表时间：
2010
期刊：
影响因子：
3.9
通讯作者：
Kehrer-Sawatzki H
中科院分区：
文献类型：
--
作者：
Roehl AC;Vogt J;Mussotter T;Zickler AN;Spöri H;Högel J;Chuzhanova NA;Wimmer K;Kluwe L;Mautner VF;Cooper DN;Kehrer-Sawatzki H
非等位基因同源重组（NAHR）是引起基因组疾病的经常性重排的原因。虽然减数分裂NAHR已在多种情况下进行了研究，但对有丝分裂NAHR知之甚少，尽管其对肿瘤发生的重要性。由于2NF 1型微缺失经常由有丝分裂NAHR引起，因此它们代表了研究有丝分裂NAHR特征的良好模型。我们使用微卫星分析和SNP阵列来区分各种不同的重组可能性，从而确定18个2型NF 1缺失中的17个，在SUZ 12基因及其高度同源的假基因中具有断点，起源于染色体内重组。这种高比例的染色体内NAHR导致体细胞2型NF 1缺失与染色体间起源的生殖系1型NF 1微缺失形成对比，其断点位于NF 1-REP（位于SUZ 12序列附近的低拷贝重复序列）内。此外，减数分裂NAHR导致的1 NF 1型缺失发生在以高GC含量和DNA双链体稳定性为特征的重组热点内，而与本文研究的有丝分裂NAHR事件相关的2型断点不在热点内聚集，并且位于GC含量和DNA稳定性显著较低的区域内。因此，我们的研究结果指出，根本的机制之间的差异，有丝分裂和减数分裂NAHR的决定因素。Mutat 31：1163-1173，2010.© 2010 Wiley利斯公司
Nonallelic homologous recombination (NAHR) is responsible for the recurrent rearrangements that give rise to genomic disorders. Although meiotic NAHR has been investigated in multiple contexts, much less is known about mitotic NAHR despite its importance for tumorigenesis. Because type‐2NF1microdeletions frequently result from mitotic NAHR, they represent a good model in which to investigate the features of mitotic NAHR. We have used microsatellite analysis and SNP arrays to distinguish between the various alternative recombinational possibilities, thereby ascertaining that 17 of 18 type‐2NF1deletions, with breakpoints in theSUZ12gene and its highly homologous pseudogene, originated via intrachromosomal recombination. This high proportion of intrachromosomal NAHR causing somatic type‐2NF1deletions contrasts with the interchromosomal origin of germline type‐1NF1microdeletions, whose breakpoints are located within the NF1‐REPs (low‐copy repeats located adjacent to theSUZ12sequences). Further, meiotic NAHR causing type‐1NF1deletions occurs within recombination hotspots characterized by high GC‐content and DNA duplex stability, whereas the type‐2 breakpoints associated with the mitotic NAHR events investigated here do not cluster within hotspots and are located within regions of significantly lower GC‐content and DNA stability. Our findings therefore point to fundamental mechanistic differences between the determinants of mitotic and meiotic NAHR. Hum Mutat 31:1163–1173, 2010. © 2010 Wiley‐Liss, Inc.
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影响因子：
5.2
作者：
Malapit CA;Caldwell DR;Sassu N;Milbin S;Howell AR
通讯作者：
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影响因子：
14.5
作者：
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对22q11.2中的减数分裂重组分析，该区域经常经历缺失和重复。
影响因子：
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作者：
Torres-Juan, Laura;Rosell, Jordi;Sanchez-de-la-Torre, Manuel;Fibla, Joan;Heine-Suner, Damia
通讯作者：
Heine-Suner, Damia
影响因子：
6.5
作者：
Steinmann, Katharina;Kluwe, Lan;Kehrer-Sawatzki, Hildegard
通讯作者：
Kehrer-Sawatzki, Hildegard
2 型 NF1 缺失非常不寻常，因为不存在非等位基因同源重组热点并且明显偏好雌性有丝分裂重组。
影响因子：
9.8
作者：
Katharina Steinmann;D. Cooper;L. Kluwe;N. Chuzhanova;C. Senger;E. Serra;C. Lázaro;M. Gilaberte;K. Wimmer;V. Mautner;H. Kehrer
通讯作者：
H. Kehrer