A Dynamic population of prophase CENP-C is required for meiotic chromosome segregation

Abstract

The centromere is an epigenetic mark that is a loading site for the kinetochore during meiosis and mitosis. This mark is characterized by the H3 variant CENP-A, known as CID in Drosophila, which replaces canonical H3 at the centromeres. In Drosophila, CENP-C is critical for maintaining CID at the centromeres and directly recruits outer kinetochore proteins after nuclear envelope break down. It is not clear, however, if these two functions require the same population of CENP-C. In Drosophila and many other metazoan oocytes, centromere maintenance and kinetochore assembly are separated by an extended prophase. We used RNAi knockdown, mutants, and transgenes to study the dynamics and function of CENP-C in meiosis. CENP-C that is incorporated into cells prior to the onset of meiosis is involved in centromere maintenance and CID recruitment. We found this is not sufficient for the other functions of CENP-C. Indeed, CENP-C is loaded during meiotic prophase, while CID and the chaperone CAL1 are not. CENP-C prophase loading is required for meiotic functions at two different times. In early meiotic prophase, CENP-C loading is required for sister centromere cohesion and centromere clustering. In late meiotic prophase, CENP-C loading is required to recruit kinetochore proteins. Thus, CENP-C is one of the few proteins that links the function of the centromeres and kinetochores through the long prophase pause in oocytes.