Cold-Shock and the Mammalian Cell Cycle

Progression through the cell cycle is temperature sensitive, but the relationship is not straightforward. In culture, many types of mammalian cells fail to undergo the G(2)/M transition after cooling from 37 degrees C to 16-20 degrees C (moderate hypothermia). However, progression through G(1) and S is not blocked at these temperatures, nor is progression through mitosis in cells cooled after they have become committed to the division process. Thus, at least one pathway is present during G(2)-but not during G(1), S or mitosis-that is selectively disrupted at or below a critical temperature. As a result, a prolonged (24-48 hr) exposure to moderate hypothermia can be used to enrich cultures for G(2) cells. A brief (1 hr) exposure to severe hypothermia (4-10 degrees C) is also reported to induce a high degree of mitotic synchrony (up to 80%) in some mammalian cultures. Although the mechanism behind this synchronization remains vague, it may involve a cell cycle checkpoint, triggered in response to the cold shock, that transiently inhibits the G(1)/S transition.