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Dannel McCollum, Ph.D.Academic Role: Associate Professor
Faculty Appointment(s) In:
Other Affiliation(s):
Molecular Mechanisms which Regulate Cytokinesis
The primary interest of my lab is understanding the molecular mechanisms which coordinate mitosis with cell division (cytokinesis). Proper regulation of cytokinesis is critical for a number of reasons. Normally cytokinesis is tightly coupled to the completion of mitosis. If cells either loose this coupling, or have defects in cytokinesis, genetic instability can result, often leading to genetic defects and cancer. We have chosen the fission yeast, Schizosaccharomyces pombe, as a model system for these studies because of the powerful molecular genetics available in S. pombe and the fact that the mechanisms of cytokinesis and cell cycle control are highly conserved between S. pombe and higher eukaryotic cells. Through the combined use of genetic biochemical and cytological techniques, we have identified a novel signal transduction pathway which functions to coordinate cell division and mitosis. This pathway (the SIN pathway) includes 4 protein kinases and one small GTPase, and functions to transmit a signal from the spindle poles to the cell division site causing initiation of cell division. Recent studies have characterized the order of function of the proteins in the pathway and revealed key mechanisms by which signaling through the pathway is regulated to ensure that cytokinesis is coupled to the other events of mitosis. For example, we recently showed that the Dma1 protein is required to inhibit the SIN in response to mitotic spindle defects to ensure that cytokinesis does not take place when chromosomes are unable to be segregated. Interestingly a human homolog of Dma1 (CHFR) is deleted in a large percent of tumors suggesting that regulation of an analogous pathway may be important to inhibit tumor formation. 
Recent PublicationsJin, Q.-W., Ray, S., Choi, S.H., and McCollum, D. (2007). The nucleolar Net1/Cfi1-related protein Dnt1 inhibits the septation initiation network in fission yeast. Mol. Biol. Cell. 18:2924-34.
Jin, Q.-W., Zhou, M, Bimbo, A, Balasubramanian, M. K. and McCollum, D. (2006). A role for the septation initiation network in septum assembly revealed by genetic analysis of sid2-250 suppressors. Genetics. 172:2101-12.
McCollum, D. (2005) Cytokinesis: Breaking the ties that bind. Curr. Biol. 15:R998-R1000.
Trautmann, S., and McCollum, D. (2005) Subcellular targeting of the S. pombe Cdc14-like phosphatase Clp1p/Flp1p reveals distinct nuclear and cytoplasmic functions and suggests a role for nuclear shuttling in Clp1p regulation. Curr. Biol. 15:1384-1389. Trautmann, S., Rajagopalan, S., and McCollum, D. (2004) The S. pombe Cdc14-like phosphatase Clp1p regulates chromosome bi-orientation and interacts with aurora kinase. Dev. Cell. Trautmann, S., Rajagopalan, S., and McCollum, D. Dev. Cell. 7:755-62 McCollum, D. (2004) Cytokinesis: The central spindle takes center stage. Curr. Biol. 14:R953-5 . Mishra M, Karagiannis, J., Trautmann, S., Wang, H., McCollum, D. , Balasubramanian , M.K. (2004). The Clp1p/Flp1p phosphatase ensures completion of cytokinesis in response to minor perturbation of the cell division machinery in Schizosaccharomyces pombe. J Cell Sci. 117:3897-910. Mitra, P., Zhang, Y., Rameh, L., Ivshina, M., McCollum, D., Nunnari, J., Hendricks, G., Kerr, M., Field, S., Cantley, L., and Ross, A. (2004). A Novel Phosphatidylinositol(3,4,5)P3 Pathway in Fission Yeast. J. Cell Biol. 166:205-11. Hou, M.-C., Guertin, D.A., and McCollum, D.(2004) Initiation of Cytokinesis is Controlled through Multiple Modes of Regulation of the Sid2p-Mob1p Kinase Complex. Mol. Cell. Biol. 24:3262-3276. Jin, Q.-W., and McCollum, D. (2003) Scw1p antagonizes the septation initiation network to regulate septum formation and cell separation in fission yeast. Euk. Cell. 2:510-520. Hou, M.C., Wiley, D.J., Verde, F., and McCollum, D . (2003). Mob2p interacts with Orb6p kinase to promote coordination of cell polarity with the cell cycle progression. J. Cell Sci. 116:125-35. Guertin, D.A., Venkatram, S., Gould, K.L., and McCollum D. (2002). Dma1p prevents mitotic exit and cytokinesis by inhibiting the Septation Initiation Network (SIN). Dev. Cell. 3:779-790. McCollum, D. (2002). First things first: Spindle orientation and mitotic progression. Nat. Cell. Biol. 4: E226-E226. Trautmann, S., and McCollum, D. (2002). Cell cycle: New functions for Cdc14 family phosphatases. Curr. Biol. 12:R733-R735. McCollum, D. (2002). Coordinating Cytokinesis and Nuclear Division in S. pombe. ASM News. 68:325-329. Guertin, D., Trautmann, S., and McCollum. D. (2002). Regulation of cytokinesis in eukaryotes. Mol. Microbiol. Rev. 66:155-178. Hou, M.C., and McCollum, D. (2002). Cytokinesis: Myosin spots the ring. Curr. Biol. 12:R334-R336. Guertin, D., and McCollum D. (2001). Interaction between the non-catalytic region of Sid1p kinase and Cdc14p is required for localization and full catalytic activity of Sid1p. J. Biol. Chem. 276:28185-189. Trautmann, S., Wolfe, B.A., Jorgensen, P., Tyers, M., Gould K.L., and McCollum. D. (2001). Fission yeast Clp1p phosphatase regulates G2/M transition and coordination of cytokinesis with cell cycle progression. Curr. Biol. 11:931-940. McCollum, D., and Gould, K. (2001). Timing is everything: regulation of mitotic exit and cytokinesis by the MEN and SIN. TrendsCell. Biol. 11:89-95. Sluder G, McCollum D. (2000). The mad ways of meiosis. Science. 289:254-255. Hou, M.C., and McCollum, D. (2000). Mob1p interacts with the Sid2p kinase and is required for cytokinesis in fission yeast. Curr. Biol. 10:619-622. Guertin, D., Chang, L., Irshad, F., Gould, K.L., and McCollum, D. (2000). The role of the Sid1p kinase and Cdc14p in a novel signaling pathway that regulates the onset of cytokinesis in fission yeast. EMBO J. 19:1803-1815. Balasubramanian, M.K., McCollum, D., and Surana, U. (2000). Tying the knot: linking cytokinesis to the nuclear cycle. J. Cell Sci. 113:1503-1513. Liu, J., Wang, H., McCollum, D., Balasubramanian, M.K. (1999). Drc1p/Cps1p, a 1,3-beta-glucan synthase subunit, is essential for division septum assembly in schizosaccharomyces pombe. Genetics. 153:1193-203. McCollum, D., Balasubramanian, M., and Gould, K.L. (1999). Isolation of cold-sensitive actin mutants defective for cytokinesis and polarized cell growth in Fission Yeast. FEBS Lett. 451:321-326. Sparks, C.A., Morphew, M., and McCollum, D . (1999). Sid2p, a spindle pole body kinase that regulates the onset of cytokinesis. J. Cell Biol. 146:777-790. McCollum, D., Feoktistova, A., and Gould, K.L. (1999). Phosphorylation of the myosin-II light chain does not regulate the timing of mitosis in fission yeast. J. Biol. Chem. 274:17691-17695. Feoktistova, A., McCollum, D., Ohi, R., and Gould, K. L. (1999). Identification and characterization of Schizosaccharomyces pombe asp1+, a gene which interacts with mutations in the Arp2/3 complex and actin. Genetics. 152:895-908. Bähler, J., Steever, A.B., Wheatley, S., Wang, Y-L., Pringle, J.R., Gould K.L., and McCollum, D. (1998). Role of polo kinase and Mid1p in determining the site of cell division in fission yeast. J. Cell Biol. 143:1603-1616. Balasubramanian, M.K., McCollum, D., Wong, K.C.Y., He, X., Sazer, S., and Gould, K.L. (1998). Isolation and characterization of new fission yeast cytokinesis mutants. Genetics. 149:1265-1275. Balasubramanian, MK, McCollum, D., Gould, KL. (1997). Cytokinesis in fission yeast Schizosaccharomyces pombe. Methods Enzymol. 283:494-506. Balasubramanian, M., Feoktistova, A., McCollum, D., and Gould, K.L. (1996). Sop2, a novel and evolutionarily conserved protein, interacts with profilin and the actin-related protein Arp3 in Fission Yeast. EMBO J. 15: 6426-6437. McCollum, D., Feoktistova, A., Morphew M., Balasubramanian, M., and Gould, K.L. (1996). The Schizosaccharomyces pombe actin related protein arp3 is part of a high molecular weight cortical complex which interacts with profilin and actin. EMBO J. 15: 6438-6446. McCollum, D., Balasubramanian, M.K., Pelcher, L.E., Hemmingsen, S., and Gould, K.L. (1995) The Schizosaccharomyces pombe cdc4+ gene encodes a novel EF-hand protein essential for cytokinesis. J. Cell Biol. 130: 651-660. Ohi, R., McCollum, D., Hirani, B., Den Haese, G., Zhang, X., Burke, J. D., Turner, K., and Gould, K. L. (1994). The Schizosaccharomyces pombe cdc5+ gene encodes an essential protein with homology to c-Myb. EMBO J. 2: 471-483.
Rotation ProjectsLittle is known about how the SID pathway monitors mitosis to ensure that cytokinesis is not initiated until mitosis is complete. We have begun to examine the function of homologs of the SID pathway genes in animal cells using RNA interference (RNAi) to disrupt their function. A potential project, would be to disrupt the function of one of the SID pathway genes and characterize its function in animal cells. We have also carried out a genetic suppressor screen to identify potential inhibitors of the SID pathway, and another potential project would be to characterize and clone one of these SID pathway inhibitory genes. A new project in the lab has involved characterization of a highly conserved protein phosphatase, which we have shown is required to inhibit progression into the next cell cycle if cytokinesis is incomplete. One project could involve examination of how this phosphatase inhibits cell cycle progression using biochemical and cytological approaches. Lab Personnel
Academic BackgroundDan McCollum received his B.S. in Biochemistry from the University of Illinois in 1987, and his Ph.D., from the University of California at San Diego in 1993. He did his postdoctoral training in Dr. Kathleen Gould's lab at Vanderbilt University. Dr. McCollum joined the faculty at the Worcester Foundation for Biomedical Research in 1996, and then joined the University of Massachusetts Medical School in the department of Molecular Genetics and Microbiology in 1997. Dr. McCollum is also a member of the Program in Cell Dynamics.
Office: Biotech4 Suite 332
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