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As a new generation of mutants begins maturing across the globe, a long-lost Master Mold A.I. and Sentinel production facility in the jungles of Ecuador is uncovered by a mysterious woman called Cassandra Nova. She uses the last surviving relative of Bolivar Trask to gain control of the wild sentinels and send several to demolish and level the mutant nation of Genosha, before being subdued by Cyclops and Wolverine.
Miraculously, teacher Emma Frost survives the attack by way of a new Secondary Mutation. At the X-Mansion, Beast investigates the biological origins of the powerful enemy they have just captured, while also revealing the possibility of mankind's genetic extinction within the next few generations. When Cassandra suddenly overcomes her imprisonment and effortlessly strolls her way to to Cerebra (in order to take over Professor X's mind), Emma Frost deftly snaps her neck, followed by the professor firing five bullets through the being's regenerating body.
In the aftermath of the attack, Emma Frost joins the X-Men, Scott and Jean explore the tensions in their relationship, and the professor officially outs himself as a mutant on national television. With more students entering the school and protesters massing outside the gates, Professor X makes the radical decision to leave the school and re-unite with Empress Lilandra. While investigating the DNA of Cassandra Nova's body, however, Dr. McCoy discovers that she shares the exact same DNA with Charles Xavier. The professor reveals that he is actually possessed by the Cassandra Nova entity (Nova switched bodies with Xavier before Emma snapped the Nova body's neck), and mentally tortures Beast before forcing a new student, Beak, to severely beat him with an aluminum baseball bat, leaving Beast in a coma and Beak catatonic.
The story arc ends with Cassandra Nova in possession of the professor's body, and leaving Earth to lay waste to the Shi'ar Imperium.