Abstract

My group has been studying the regulation of mitosis by the Spindle Assembly Checkpoint (SAC), by exploiting the genetics and cell biology of Drosophila. We have recently been focusing on two components of the SAC , Mad1 and RZZ . Proper recruitment of Mad1 to unattached kinetochores requires the RZZ complex, by a mechanism that remains to be elucidated.

The more we study these proteins, the more surprises they offer up. My talk will have two parts. First I will describe an interesting point mutation in the RZZ subunit Rod that appears to block RZZ and Mad1 recruitment in early syncytial embryos but not later in development, suggesting that kinetochores may possess some stage- or tissue-specific properties. I will then focus on Mad1 and the evidence we have accumulated that this classical spindle checkpoint protein has an additional role in interphase nuclei quite unrelated to mitosis. Mad1, unlike Mad2, is present in all nuclei of Drosophila, including postmitotic tissues. Mad1 associates with a set of proteins potentially involved in chromatin organization. These proteins colocalize with Mad1 in Intranuclear Territories (“MINTs” ) In spermatocytes, where chromatin is structured into three well-spaced masses, one can see these MIN Ts particularly clearly. Removal of Mad1 affects both the intranuclear localization of these partner proteins and chromatin packaging. The mitotic phenotype of a mad1 null may therefore reflect not just a defective spindle checkpoint but also consequences of aberrant interphase chromatin organization.