Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Bioessays. 2017 Sep;39(9). doi: 10.1002/bies.201700073. Epub 2017 Aug 9.
The functions of the Bloom syndrome helicase (BLM) and its orthologs are well characterized in mitotic DNA damage repair, but their roles within the context of meiotic recombination are less clear. In meiotic recombination, multiple repair pathways are used to repair meiotic DSBs, and current studies suggest that BLM may regulate the use of these pathways. Based on literature from Saccharomyces cerevisiae, Arabidopsis thaliana, Mus musculus, Drosophila melanogaster, and Caenorhabditis elegans, we present a unified model for a critical meiotic role of BLM and its orthologs. In this model, BLM and its orthologs utilize helicase activity to regulate the use of various pathways in meiotic recombination by continuously disassembling recombination intermediates. This unwinding activity provides the meiotic program with a steady pool of early recombination substrates, increasing the probability for a DSB to be processed by the appropriate pathway. As a result of BLM activity, crossovers are properly placed throughout the genome, promoting proper chromosomal disjunction at the end of meiosis. This unified model can be used to further refine the complex role of BLM and its orthologs in meiotic recombination.
布卢姆综合征解旋酶(BLM)及其同源物的功能在有丝分裂 DNA 损伤修复中得到了很好的描述,但它们在减数分裂重组背景下的作用尚不清楚。在减数分裂重组中,多种修复途径被用于修复减数分裂 DSB,目前的研究表明,BLM 可能调节这些途径的使用。基于来自酿酒酵母、拟南芥、小家鼠、黑腹果蝇和秀丽隐杆线虫的文献,我们提出了 BLM 及其同源物在减数分裂中的关键作用的统一模型。在这个模型中,BLM 和它的同源物利用解旋酶活性通过不断拆解重组中间体来调节减数分裂重组中各种途径的使用。这种解旋活性为减数分裂程序提供了稳定的早期重组底物池,增加了 DSB 通过适当途径被处理的概率。由于 BLM 的活性,交叉被正确地放置在整个基因组中,促进减数分裂结束时染色体的正确分离。这个统一的模型可以用来进一步细化 BLM 和它的同源物在减数分裂重组中的复杂作用。