Abstract
As the third domain of life, archaea, like the eukarya and bacteria, must have robust DNA replication and repair complexes to ensure genome fidelity. Archaea moreover display a breadth of unique habitats and characteristics, and structural biologists increasingly appreciate these features. As archaea include extremophiles that can withstand diverse environmental stresses, they provide fundamental systems for understanding enzymes and pathways critical to genome integrity and stress responses. Such archaeal extremophiles provide critical data on the periodic table for life as well as on the biochemical, geochemical, and physical limitations to adaptive strategies allowing organisms to thrive under environmental stress relevant to determining the boundaries for life as we know it. Specifically, archaeal enzyme structures have informed the architecture and mechanisms of key DNA repair proteins and complexes. With added abilities to temperature-trap flexible complexes and reveal core domains of transient and dynamic complexes, these structures provide insights into mechanisms of maintaining genome integrity despite extreme environmental stress. The DNA damage response protein structures noted in this review therefore inform the basis for genome integrity in the face of environmental stress, with implications for all domains of life as well as for biomanufacturing, astrobiology, and medicine.
Highlights
From the ideas of Lamarck, to Darwin and Mendel, to Huxley and those involved in the modern evolutionary synthesis, the accepted views behind the driving force of inheritance and evolution have certainly themselves “evolved” over time
In the mid-1800s, Haeckel expanded these categorical divisions of life, which, by the 1960s, eventually grew to 5 “Kingdoms,” allowing the Monera, Protista, and Fungi to be positioned alongside the Animalia and Plantae [1, 2]
We will highlight informative examples where archaeal genome maintenance protein structures were found to be more similar in organization to eukaryal structures than to bacterial or perhaps provide more insights into how protein structures impact human health, where the first or only structure(s) of a particular protein system was derived from archaea
Summary
From the ideas of Lamarck, to Darwin and Mendel, to Huxley and those involved in the modern evolutionary synthesis, the accepted views behind the driving force of inheritance and evolution have certainly themselves “evolved” over time. We will highlight informative examples where archaeal genome maintenance protein structures were found to be more similar in organization to eukaryal structures than to bacterial or perhaps provide more insights into how protein structures impact human health, where the first or only structure(s) of a particular protein system was derived from archaea. In all these cases structural results on archaeal proteins are important cornerstones for understanding human homologs involved in disease. As human cell genetics and biological tools improve along with structural results, data from human system and archaeal systems will further complement each other to provide a deeper and more unified understanding as illustrated for FEN1-PCNA, Mre11Rad, Rad, and XPD systems that are among the examples presented here
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