Mechanisms of Recombination between Diverged Sequences in Wild-Type and BLM-Deficient Mouse and Human Cells

Jeannine R. LaRocque; Maria Jasin

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Mechanisms of Recombination between Diverged Sequences in Wild-Type and BLM-Deficient Mouse and Human Cells

机译：野生型和BLM缺陷型小鼠和人类细胞中不同序列之间的重组机制

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Double-strand breaks (DSBs) are particularly deleterious DNA lesions for which cells have developed multiple mechanisms of repair. One major mechanism of DSB repair in mammalian cells is homologous recombination (HR), whereby a homologous donor sequence is used as a template for repair. For this reason, HR repair of DSBs is also being exploited for gene modification in possible therapeutic approaches. HR is sensitive to sequence divergence, such that the cell has developed ways to suppress recombination between diverged (“homeologous”) sequences. In this report, we have examined several aspects of HR between homeologous sequences in mouse and human cells. We found that gene conversion tracts are similar for mouse and human cells and are generally ≤100 bp, even in Msh2?/? cells which fail to suppress homeologous recombination. Gene conversion tracts are mostly unidirectional, with no observed mutations. Additionally, no alterations were observed in the donor sequences. While both mouse and human cells suppress homeologous recombination, the suppression is substantially less in the transformed human cells, despite similarities in the gene conversion tracts. BLM-deficient mouse and human cells suppress homeologous recombination to a similar extent as wild-type cells, unlike Sgs1-deficient Saccharomyces cerevisiae.

机译：双链断裂（DSB）是特别有害的DNA损伤，其细胞已发展出多种修复机制。哺乳动物细胞中DSB修复的一种主要机制是同源重组（HR），其中同源供体序列用作修复模板。因此，在可能的治疗方法中，也正在利用DSB的HR修复技术进行基因修饰。 HR对序列分歧敏感，因此细胞已开发出抑制分歧（“同源”）序列之间重组的方法。在本报告中，我们研究了小鼠和人类细胞中同源序列之间HR的几个方面。我们发现，即使在 Msh2 ？ / ？中，小鼠和人类细胞的基因转换通道也相似，且通常≤100 bp。无法抑制同源重组的细胞。基因转换道大部分是单向的，没有观察到突变。另外，在供体序列中未观察到改变。尽管小鼠和人类细胞均抑制同源重组，但是尽管基因转化途径相似，但在转化的人类细胞中抑制作用却要小得多。缺乏BLM的小鼠和人类细胞抑制同源重组的程度与野生型细胞相似，这与缺乏Sgs1的酿酒酵母不同。 展开▼

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《Molecular and Cellular Biology》 |2010年第8期|共11页

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Jeannine R. LaRocque; Maria Jasin;
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中图分类细胞生物学;

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1. Mechanisms of Recombination between Diverged Sequences in Wild-Type and BLM-Deficient Mouse and Human Cells [J] . Jeannine R. LaRocque, Maria Jasin Molecular and Cellular Biology . 2010,第8期

机译：野生型和BLM缺陷型小鼠和人类细胞中不同序列之间的重组机制

2. Intrachromosomal recombination between highly diverged DNA sequences is enabled in human cells deficient in Bloom helicase [J] . Wang Yibin, Li Shen, Smith Krissy, DNA repair . 2016,第Null期

机译：缺乏布鲁姆解旋酶的人类细胞能够实现高度差异化的DNA序列之间的染色体内重组

3. EXO1 suppresses double-strand break induced homologous recombination between diverged sequences in mammalian cells [J] . Chen Chun-Chin, Avdievich Elena, Zhang Yongwei, DNA repair . 2017,第期

机译：EXO1抑制双链断裂诱导哺乳动物细胞中发散序列之间的同源重组

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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6. Mechanisms of Recombination between Diverged Sequences in Wild-Type and BLM-Deficient Mouse and Human Cells [O] . Jeannine R. LaRocque, Maria Jasin 2010

机译：野生型和BLM缺陷型小鼠和人类细胞中不同序列之间的重组机制

7. Mechanisms of Recombination between Diverged Sequences in Wild-Type and BLM-Deficient Mouse and Human Cells ▿ † [O] . LaRocque, Jeannine R., Jasin, Maria 2010

机译：野生型和BLM缺陷型小鼠和人类细胞中不同序列之间的重组机制▿†

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6. 野生型和功能缺陷型的RANTES Intrakine转化的人外周血T细胞的抗HIV-1作用 [C] . 杨安钢 ,Xia Zhang . 第七次全国基因结构表达与调控学术讨论会 . 1999

7. 人类免疫缺陷病毒1型Tat不同突变体重组蛋白的构建及其免疫原性和抗原性分析 [A] . 张华群 . 2011

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3. Processes for producing a recombinant serine protease inhibitor modulating a serine protease to diagnose patients suspected of having a mutation in a gene encoding a serine protease inhibitor to treat a condition associated with serine proteases in a patient and inhibit the molecular mechanisms and inflammation and reduce tissue damage in a cell or tissue composition capable of effectively modulating serine-protease activity using the human wild-type a-1-anti-chymotrypsin analog composition nucleic acid sequence host cell expression vector and preparation of protin [P] . 外国专利： BR9507467A . 1997-09-23

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4. DNA was isolated and purified, peptu00ecdeo, sequences of amino acids of human and murine sphk2, construction of recombinant DNA, host cell.Methods for producing a peptu00ecdeo of sphingosine kinase type 2 isoform of mouse and human.And to detect an agent or a drug that inhibits or promotes the activity of sphingosine kinase type 2, agent or product, methods for regulating a biological process in a mamu00ecfero,For the treatment or the improvement of a disease resulting from cell death increased or reduced cell proliferation.For the treatment or management of a disease resulting from reduced cell death or cell proliferation increased.And for the treatment or the improvement of a disease resulting from abnormal migration or motility of cells selected from the group consisted of cancer, restenose and diabetic neuropathy.Composition for the treatment or the improvement of UIMA disease resulting from cell death increased or reduced cell proliferation.Methods for screening for agents or [P] . 外国专利： BR0109827A . 2004-07-06

机译：分离纯化DNA，肽，人和鼠sphk2的氨基酸序列，重组DNA的构建，宿主细胞。小鼠和人2型鞘氨醇激酶2型亚型的肽的制备方法，并检测抑制或促进2型鞘氨醇激酶活性的药物或药物，药物或产物的调节方法，用于治疗哺乳动物的生物学过程的方法，用于治疗或改善由细胞死亡引起的疾病的方法，增加或减少的细胞增殖用于治疗或管理由减少的细胞死亡或细胞增殖引起的疾病，以及用于治疗或改善由癌症，再狭窄和糖尿病性神经病变组成的组中的细胞异常迁移或运动导致的疾病。用于治疗或改善由细胞死亡引起的UIMA疾病的组合物可增加或减少细胞增殖。

5. FAB Region Genes and Sequences of Mouse Aggregated Monoclonal Antibodies Against Human Blood Cells [P] . 外国专利： KR100263438B1 . 2000-08-01

机译：小鼠抗人血细胞单克隆抗体的FAB区基因和序列

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Mechanisms of Recombination between Diverged Sequences in Wild-Type and BLM-Deficient Mouse and Human Cells

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