de Bruin Robertus A M, Kalashnikova Tatyana I, Chahwan Charly, McDonald W Hayes, Wohlschlegel James, Yates John, Russell Paul, Wittenberg Curt
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Mol Cell. 2006 Aug;23(4):483-96. doi: 10.1016/j.molcel.2006.06.025.
G1-specific transcription in yeast depends upon SBF and MBF. We have identified Nrm1 (negative regulator of MBF targets 1), as a stable component of MBF. NRM1 (YNR009w), an MBF-regulated gene expressed during late G1 phase, associates with G1-specific promoters via MBF. Transcriptional repression upon exit from G1 phase requires both Nrm1 and MBF. Inactivation of Nrm1 results in prolonged expression of MBF-regulated transcripts and leads to hydroxyurea (HU) resistance and enhanced bypass of rad53Delta- and mec1Delta-associated lethality. Constitutive expression of a stabilized form of Nrm1 represses MBF targets and leads to HU sensitivity. The fission yeast homolog SpNrm1, encoded by the MBF target gene nrm1(+) (SPBC16A3.07c), binds to MBF target genes and acts as a corepressor. In both yeasts, MBF represses G1-specific transcription outside of G1 phase. A negative feedback loop involving Nrm1 bound to MBF leads to transcriptional repression as cells exit G1 phase.
酵母中的G1期特异性转录依赖于SBF和MBF。我们已鉴定出Nrm1（MBF靶标1的负调控因子）是MBF的一个稳定成分。NRM1（YNR009w）是一个在G1期晚期表达的受MBF调控的基因，它通过MBF与G1期特异性启动子结合。从G1期退出时的转录抑制需要Nrm1和MBF两者。Nrm1的失活导致MBF调控转录本的持续表达，并导致对羟基脲（HU）产生抗性，以及增强对与rad53Δ和mec1Δ相关的致死性的绕过。稳定形式的Nrm1的组成型表达会抑制MBF靶标，并导致对HU敏感。由MBF靶标基因nrm1⁺（SPBC16A3.07c）编码的裂殖酵母同源物SpNrm1与MBF靶标基因结合，并作为一个共抑制因子发挥作用。在这两种酵母中，MBF在G1期之外抑制G1期特异性转录。当细胞退出G1期时，一个涉及与MBF结合的Nrm1的负反馈环导致转录抑制。
