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The study of planktic and benthic δ18O at site U1389 in the Gulf of Cadiz allowed us to reconstruct climate variability during the penultimate glacial period at an unprecedented millennial scale resolution. Hereby, a sequence of interstadial-stadial episodes similar to the Dansgaard-Oeschger events recorded during Marine Isotope Stage (MIS)3, were recognized in MIS6. After a detailed correlation with millennial-scale variability recorded along the Iberian margin and the North Atlantic we were able to link the millennial changes next to the Iberian Peninsula with Antarctic climate variability due to the interhemispheric seesaw response of the Atlantic circulation. The straight coupling at site U1389 of a) the planktic δ18O that reflects climate change in the Atlantic with b) the benthic δ18O, which records the temperature and oxygen isotope composition of the mixture of Mediterranean Outflow and Atlantic intermediate water, indicates that millennial climate variability also had a strong impact on the eastern Mediterranean. The detailed analysis of the benthic δ13C and the fine sand content in the sediments from site U1389 led us to recognize the response of the Mediterranean overflow water (MOW) to millennial scale changes in Mediterranean overturning circulation during the penultimate glaciation. Both Mediterranean Overturning Circulation and MOW strength increased at times of cool and arid climates and weakened during warm and more humid episodes, similar to what has been described for MIS3. The tuning of MOW weakening events occurring at times of precession minima with eastern Mediterranean sapropels and enhanced Asian monsoon allowed the elaboration of a new chronology for MIS6. It was compared with the Epica Dome C time scale, which was also based on the tuning of atmospheric δ18O with Asian Monsoons speleothem records. Mediterranean overturning during MIS6 was also strongly affected by freshwater perturbations occurring at times of insolation maxima, leading to the formation of the "glacial sapropel" S6. Two major drops in seawater δ18O centered at 175 and 150 ky were observed near the entrance of the Mediterranean that were related to meltwater released from the ice sheets, coinciding with periods of insolation maxima. The entry of this meltwater anomaly through the Strait of Gibraltar is clearly registered in the western and eastern Mediterranean, especially at the onset of sapropel S6, suggesting that it was a major component of the freshwater that initiated the buoyancy gain preceding deep water stagnation. • Stadial/interstadial episodes were observed in MIS6 similar to Dansgaard-Oeschger events. • Mediterranean overflow revealed millennial climate change in the Mediterranean in MIS6. • Meltwater from Ice Sheets contributed to Mediterranean stagnation during "glacial sapropels". [ABSTRACT FROM AUTHOR]