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减数分裂重组热点:塑造基因组及对高变微卫星DNA变化的见解

Meiotic recombination hotspots: shaping the genome and insights into hypervariable minisatellite DNA change.

作者信息

Wahls W P

机构信息

Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.

出版信息

Curr Top Dev Biol. 1998;37:37-75. doi: 10.1016/s0070-2153(08)60171-4.

Abstract

Meiotic homologous recombination serves three principal roles. First, recombination reassorts the linkages between newly-arising alleles to provide genetic diversity upon which natural selection can act. Second, recombination is used to repair certain types of DNA damage to provide a mechanism of genomic homeostasis. Third, with few exceptions homologous recombination is required for the appropriate segregation of homologous chromosomes during meiosis. Recombination rates are elevated near DNA sites called "recombination hotspots." These sites influence the distribution of recombination along chromosomes and the timing of recombination during the life cycle. Recent advances have revealed biochemical steps of hotspot activation and have suggested that hotspots may regulate when and where recombination occurs. Two models for hotspot activation, one in which hotspots act early in the recombination pathway and one in which hotspots act late in the recombination pathway, are presented. The latter model can account for changes at hypervariable minisatellite DNA in metazoan genomes by invoking resolution of Holliday junctions at minisatellite DNA repeats.

摘要

减数分裂同源重组发挥着三个主要作用。首先,重组重新排列新出现的等位基因之间的连锁关系,以提供自然选择可以作用的遗传多样性。其次,重组用于修复某些类型的DNA损伤,以提供基因组稳态的机制。第三,除少数例外情况,减数分裂期间同源染色体的正确分离需要同源重组。重组率在称为“重组热点”的DNA位点附近升高。这些位点影响重组在染色体上的分布以及生命周期中重组的时间。最近的进展揭示了热点激活的生化步骤,并表明热点可能调节重组发生的时间和位置。本文提出了两种热点激活模型,一种是热点在重组途径早期起作用,另一种是热点在重组途径后期起作用。后一种模型可以通过调用微卫星DNA重复序列处Holliday连接的解析来解释后生动物基因组中高变微卫星DNA的变化。

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