Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5A, 02-106, Warsaw, Poland.
Sci Rep. 2024 Apr 30;14(1):9922. doi: 10.1038/s41598-024-60318-w.
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.
范可尼贫血（FA）途径可修复 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，并在真菌中被推测。FA 蛋白 FANCM、FANCL 和 FANCJ 存在于酿酒酵母中，但它们相互作用以解决 ICL 的机制仍不清楚。与 Dikarya 不同，早期分化的真菌（EDF）具有更多与动物共享的特征。我们追踪了 FA 途径在 Opisthokonta 中的进化历史。我们扫描了完整的蛋白质组，以确定 FA 相关同源物，以建立它们的分类分布，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有反应，以及它们的基因组定位是否存在潜在的共定位。我们鉴定了真菌的激活和 ID 复合物、8 个核心蛋白中的 5 个、所有的内切酶和去泛素化蛋白的同源物。所有真菌都缺乏 FANCC、FANCF 和 FANCG 蛋白，这些蛋白在动物中负责复制后修复和染色体稳定性。观察到的分类分布可以归因于 FA 途径从 EDF 到 Dikarya 的逐渐退化。一个关键的区别是，EDF 具有 ID 复合物，可将内切酶招募到 ICL 部位。此外，在 32 个鉴定出的 FA 基因中，有 21 个在不同的生长条件下上调。一些 FA 基因在真菌基因组中存在共定位，这也可能促进共表达。我们的结果表明，一个最小的 FA 途径可能仍然在 Mucoromycota 中发挥功能，而在 Dikarya 祖先中，该途径的成分逐渐丢失。
