MSA1 IS REQUIRED FOR PROPER TIMING OF G1-SPECIFIC TRANSCRIPTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In the budding yeast Saccharomyces cerevisiae, cell cycle initiation is prompted during G(1) phase by Cln3/cyclin-dependent protein kinase-mediated transcriptional activation of G(1)-specific genes. A recent screening performed to reveal novel interactors of SCB-binding factor (SBF) and MCB-binding factor (MBF) identified, in addition to the SBF-specific repressor Whi5 and the MBF-specific corepressor Nrm1, a pair of homologous proteins, Msa1 and Msa2 (encoded by YOR066w and YKR077w), as interactors of SBF and MBF, respectively. MSA1 is expressed periodically during the cell cycle with peak mRNA levels occurring at the late M/early G(1) phase and peak protein levels occurring in early G(1). Msa1 associates with SBF- and MBF-regulated target promoters consistent with a role in G(1)-specific transcriptional regulation. Msa1 affects cell cycle initiation by advancing the timing of transcription of G(1)-specific genes. Msa1 binds to SBF- and MBF-regulated promoters and binding is maximal during the G(1) phase. Binding depends upon the cognate transcription factor. Msa1 overexpression advances the timing of SBF-dependent transcription and budding, whereas depletion delays both indicators of cell cycle initiation. Similar effects on MBF-regulated transcription are observed. Based upon these results, we conclude that Msa1 acts to advance the timing of G(1)-specific transcription and cell cycle initiation.