Transcription linked to recombination: a gene-internal promoter coincides with the recombination hot spot II of the human MLL gene

S Scharf; J Zech; A Bursen; D Schraets; P L Oliver; S Kliem; E Pfitzner; E Gillert; T Dingermann; R Marschalek

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Transcription linked to recombination: a gene-internal promoter coincides with the recombination hot spot II of the human MLL gene

机译：与重组相关的转录：基因内部启动子与人MLL基因的重组热点II一致

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The MLL gene is frequently involved in chromosomal translocations associated with high-risk acute leukaemia. Infant and therapy-related acute leukaemia patients display chromosomal breakpoints preferentially clustered in the telomeric portion of the MLL breakpoint cluster region (SCII). Here, we demonstrate that SCII colocalizes with a gene-internal promoter element in the mouse and human MLL gene, respectively. The mRNA generated encodes an N-terminally truncated version of MLL that still exhibits many functional regions, including the C-terminal SET-domain. Etoposide-induced DNA double-strand breaks colocalize with the binding site of RNA polymerase II and the transcription initiation region, but not with a nearby Topo II consensus sequence. Thus, the observed genomic instability of the human MLL gene is presumably linked to transcriptional processes. The consequences of this novel finding for the creation of chromosomal translocations, the biology of the MLL protein and for MLL-mediated acute leukaemia are discussed.

机译：MLL基因经常参与与高危急性白血病相关的染色体易位。婴儿和治疗相关的急性白血病患者显示的染色体断裂点优先聚集在MLL断裂点簇区域（SCII）的端粒部分。在这里，我们证明SCII分别与小鼠和人类MLL基因中的基因内部启动子元件共定位。产生的mRNA编码的MLL的N端截短的版本仍显示出许多功能区域，包括C端SET域。依托泊苷诱导的DNA双链断裂与RNA聚合酶II的结合位点和转录起始区共定位，但与附近的Topo II共有序列共定位。因此，观察到的人MLL基因的基因组不稳定性可能与转录过程有关。讨论了这一新发现对染色体易位，MLL蛋白生物学和MLL介导的急性白血病的影响。

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《Oncogene》 |2007年第10期|共11页
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S Scharf; J Zech; A Bursen; D Schraets; P L Oliver; S Kliem; E Pfitzner; E Gillert; T Dingermann; R Marschalek;
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1. DNA structural properties of AF9 are similar to MLL and could act as recombination hot spots resulting in MLL/AF9 translocations and leukemogenesis. [J] . Strissel PL, Strick R, Tomek RJ, Human Molecular Genetics . 2000,第11期

机译：AF9的DNA结构特性与MLL相似，可作为重组热点，导致MLL / AF9易位和白血病发生。
2. Recombination hot spot in the human beta-globin gene cluster: meiotic recombination of human DNA fragments in Saccharomyces cerevisiae. [J] . D Treco, B Thomas, N Arnheim Molecular and Cellular Biology . 1985,第8期

机译：人类β-珠蛋白基因簇中的重组热点：酿酒酵母中人类DNA片段的减数分裂重组。
3. Linkage disequilibrium analysis of the human adenosine deaminase (ada) gene provides evidence for a lack of correlation between hot spots of equal and unequal homologous recombination. [J] . Cruciani F, Bernardini L, Santolamazza P, Genomics . 2003,第1期

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4. An analytic approach to the effect of recombination mechanisms on excess photograted carrier concentration in low dimensional III-V solar cells part I: auger and radiation recombination [C] . A. C. Varonides, A. W. Berger Eourpean Photovoltaic Solar Energy Conference . 2000

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5. Genomic analysis of homoeologous gene-rich recombination hot spots and molecular targeting of the Q locus in wheat. [D] . Faris, Justin D. 1999

机译：小麦同源同源基因重组热点的基因组分析和Q基因座的分子定位。
6. Recombination hot spot in the human beta-globin gene cluster: meiotic recombination of human DNA fragments in Saccharomyces cerevisiae. [O] . D Treco, B Thomas, N Arnheim 1985

机译：人类β-珠蛋白基因簇中的重组热点：酿酒酵母中人类DNA片段的减数分裂重组。
7. Transcription linked to recombination: a gene-internal promoter coincides with the recombination hot spot II of the human MLL gene. [O] . Scharf, S, Zech, J, Bursen, A, 2007

机译：与重组相关的转录：基因内部启动子与人MLL基因的重组热点II一致。

Transcription linked to recombination: a gene-internal promoter coincides with the recombination hot spot II of the human MLL gene

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