If life ever appeared on Mars and if it did refuge into sub-superficial environments when surface conditions turned too hostile, then it should have been periodically revived from the frozen, dormant state in order to repair the accumulated damage and reset the survival clock to zero for the next dormant phase. Thus, unravelling how long Earth dormant microorganisms can cope with high-LET radiation mimicking long-term irradiation is fundamental to get insights into the long-term resilience of a dormant microbial life in the Martian subsurface over geological timescales that might have taken advantage of periodically clement conditions that allowed the repair of the accumulated DNA damage. The exposure of dried cells of the radioresistant cyanobacterium Chroococcidiopsis sp. CCMEE 029 to 2 kGy of heavy-ion radiation (Fe ions) did not significantly reduce its survival, although DNA damage was accumulated. Upon rehydration, DNA lesions were repaired as suggested by the over-expression of genes involved in the repair of double strand breaks (DSBs), oxidized bases and apurinic-apyrimidinic sites. Indeed, the monitoring of repair genes upon rehydration suggested a key role of the RecF homologous recombination in repairing DSBs. While the fact that out of the eight genes of the BER system, only one was up-regulated, suggested the absence of DNA lesions generally induced by UV radiation. In conclusion, the non-significantly reduced survival of dried Chroococcidiopsis exposed to 2 kGy of Fe-ion radiation further expanded our appreciation of the resilience of a putative dormant life in the Martian subsurface. Moreover, it is also relevant when searching life on Europa and Enceladus where the radiation environment might critically affect the long-term survival of dormant, frozen life forms.

Mars exploration motivates the search for extraterrestrial life, the development of space technologies, and the design of human missions and habitations. Here, we seek new insights and pose unresolved questions relating to the natural history of Mars, habitability, robotic and human exploration, planetary protection, and the impacts on human society. Key observations and findings include:

1. – high escape rates of early Mars' atmosphere, including loss of water, impact present-day habitability;

2. – putative fossils on Mars will likely be ambiguous biomarkers for life;

3. – microbial contamination resulting from human habitation is unavoidable; and

4. – based on Mars' current planetary protection category, robotic payload(s) should characterize the local martian environment for any life-forms prior to human habitation.

Some of the outstanding questions are:

1. – which interpretation of the hemispheric dichotomy of the planet is correct;

2. – to what degree did deep-penetrating faults transport subsurface liquids to Mars' surface;

3. – in what abundance are carbonates formed by atmospheric processes;

4. – what properties of martian meteorites could be used to constrain their source locations;

5. – the origin(s) of organic macromolecules;

6. – was/is Mars inhabited;

7. – how can missions designed to uncover microbial activity in the subsurface eliminate potential false positives caused by microbial contaminants from Earth;

8. – how can we ensure that humans and microbes form a stable and benign biosphere; and

9. – should humans relate to putative extraterrestrial life from a biocentric viewpoint (preservation of all biology), or anthropocentric viewpoint of expanding habitation of space?

Studies of Mars' evolution can shed light on the habitability of extrasolar planets. In addition, Mars exploration can drive future policy developments and confirm (or put into question) the feasibility and/or extent of human habitability of space.