PDF(Pubmed)
Abstract：
Fanconi Anemia (FA) pathway resolves DNA interstrand cross links (ICL). The FA pathway was initially recognized in vertebrates, but was later confirmed in other animals and speculated in fungi. FA proteins FANCM, FANCL and FANCJ are present in Saccharomyces cerevisiae but, their mechanism of interaction to resolve ICL is still unclear. Unlike Dikarya, early diverging fungi (EDF) possess more traits shared with animals. We traced the evolutionary history of the FA pathway across Opisthokonta. We scanned complete proteomes for FA-related homologs to establish their taxonomic distribution and analyzed their phylogenetic trees. We checked transcription profiles of FA genes to test if they respond to environmental conditions and their genomic localizations for potential co-localization. We identified fungal homologs of the activation and ID complexes, 5 out of 8 core proteins, all of the endonucleases, and deubiquitination proteins. All fungi lack FANCC, FANCF and FANCG proteins responsible for post-replication repair and chromosome stability in animals. The observed taxonomic distribution can be attributed to a gradual degradation of the FA pathway from EDF to Dikarya. One of the key differences is that EDF have the ID complex recruiting endonucleases to the site of ICL. Moreover, 21 out of 32 identified FA genes are upregulated in response to different growth conditions. Several FA genes are co-localized in fungal genomes which also could facilitate co-expression. Our results indicate that a minimal FA pathway might still be functional in Mucoromycota with a gradual loss of components in Dikarya ancestors.
摘要：
范可尼贫血（FA）途径解决DNA链间交联（ICL）。FA途径最初在脊椎动物中被识别，但后来在其他动物中得到证实，并推测为真菌。FA蛋白质FANCM,FANCL和FANCJ存在于酿酒酵母中，但是，它们相互作用解决ICL的机制尚不清楚。不像Dikarya,早期发散真菌（EDF）具有更多与动物共有的性状。我们追踪了Opisthokonta上FA途径的进化史。我们扫描了与FA相关的同源物的完整蛋白质组，以建立它们的分类学分布并分析它们的系统发育树。我们检查了FA基因的转录谱，以测试它们是否对环境条件和它们的基因组定位做出反应，以进行潜在的共定位。我们鉴定了激活和ID复合物的真菌同源物，8个核心蛋白中的5个，所有的核酸内切酶,和去泛素化蛋白。所有真菌都缺乏FANCC,负责动物复制后修复和染色体稳定性的FANCF和FANCG蛋白。观察到的分类学分布可归因于FA途径从EDF到Dikarya的逐渐降解。关键差异之一是EDF具有将核酸内切酶募集到ICL位点的ID复合物。此外，响应于不同的生长条件,32个鉴定的FA基因中的21个被上调。几个FA基因共定位在真菌基因组中,这也可以促进共表达。我们的结果表明，最小的FA途径可能在粘菌中仍然起作用，而在Dikarya祖先中逐渐失去成分。
