Fission Yeast (Schizosaccharomyces pombe) as a Model System in Study of Cell Cycle G2/M Controls and Viral Infections
Fission yeast (Schizosaccharomyces pombe) is a simple, monocellular eukaryotic organism. It has been used successfully as an experimental model to study the function and expression of human genes related to various human diseases. An obvious advantage of using fission yeast as a model system is that it can be readily grown and manipulated in laboratory using a variety of sophisticated molecular and genetic methodologies. Importantly, it also shares many molecular, genetic, and biochemical features with higher eukaryotic cells, making it a particularly useful model to study the cross-species gene activities involved in highly conserved cellular processes such as cell cycle control [see Table 1; for reviews see (Zhao and Lieberman, 1995 )]. Our laboratory uses fission yeast as a model system to study the effects of HIV-1 Vpr on basic cellular functions including cell cycle G2/M control, cytoplasmic-nuclear shuffling and cellular structures. For a list of publications that uses fission yeast as a host for the study of various viral gene expressions, see Table 2.
Table 1. Homologues of fission yeast and human proteins that are involved in cell cycle G2/M control.
| Fission yeast (S. pombe) | Human (Homo sapiens) | Putative activities | References |
| Mitotic Regulators: | |||
| Cdc2 | Cdk1 | Cyclin-dependent kinase | Lee and Nurse, 1987 |
| Cdc13 | Cyclin B | B-type cyclin | |
| Wee1 | Wee1 | Tyrosine kinase | Igarashi et al., 1991 |
| Mik1 | --- | Tyrosine kinase | |
| Cdc25 | Cdc25B/C | Tyrosine phosphatase | Sadhu et al., 1990; Nagata et al., 1991 |
| DNA Damage and Replication Checkpoints: | |||
| Rad1 | hRad1 | Nuclease | Narathi et al., 1998 |
| Rad3 | ATM/ATR | Protein kinase | Bently et al., 1996 |
| Rad9 | hRad9 | 3'-5' exonuclease | Lieberman et al., 1996 |
| Rad24/25 | 14-3-3 | Binds to phosphorylated serine | Ford et al., 1994 |
| Hus1 | hHus1 | A PCNA-related protein | Volkmer et al., 1999 |
|
Crb2 |
BRCA1 | unknown | Saka et al., 1997 |
| Mrc1 | CLSPN | unknown | Tanaka et al., 2001 |
| Chk1 | Chk1 | Serine/'Threonine kinase | Furnari et al, 1997 |
| Cds1 | Chk2 | Serine/Threonine kinase | Matsuoka et al., 1998 |
| Cellular proteins that are involved in HIV-1 Vpr-induced G2 arrest | |||
| PP2A | PP2A | Protein phosphotase 2A | Kinoshita et al., 1990 |
| Wos2 | P23 | Weel inhibitor | Munoz et al., 1999 |
| Rhp23 | HHR23A/B | Excision DNA repair enzyme | Zhao et al., 2002 |
Our goal is to use S. pombe as a model system to study the effects of HIV-1 Vpr on basic cellular functions and the role of Vpr in viral pathogenesis. The function of HIV vpr gene has been linked to viral activation and depletion of human CD4 lymphocyte, which are the major clinical manifestation of AIDS. This gene is also capable of altering human cell division cycle, a process that is critical for maintain genetic integrity of cells and is often linked to cell death or the cause of cancer once impaired. Our and others studies showed that expression of HIV vpr gene induces changes in fission yeast similar to those observed in human cells. For more information on the use of fission yeast as a model system to study HIV-1 Vpr, see Zhao and Elder, 2000, Elder, et al., 2002 or Zhao, Bukrinsky and Elder, 2004.
Table 2. List of papers that uses fission yeast as a host to study viral gene expressions.
| Name of the Virus | Number of References* |
| Human viruses | 111 |
| Human immunodeficiency viruses (HIV) | 35 |
| Human papillovirus (HPV) | 13 |
| Human herpes viruses (HSV) | 7 |
| Human cytomalloviruses (CMV) | 3 |
| Human hepatitis viruses (HBV or HCV) | 4 |
| Adenoviruses | 16 |
| Polyomaviruses | 7 |
| Simian virus 40 (SV40) | 6 |
| Plant viruses | 28 |
| Other viruses | 54 |
| All viruses combined | 184 |
| *, as of Jan, 2011 |
Click here to view PubMed literature on studies of viral genes in the budding yeast (Saccharomyces cerevisae)