Role of a Candida albicans Nrm1/Whi5 homologue in cell cycle gene expression and DNA replication stress response.
Role of a Candida albicans Nrm1/Whi5 homologue in cell cycle gene expression and DNA replication stress response.
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DOI：
10.1111/j.1365-2958.2012.08056.x
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发表时间：
2012-05
影响因子：
3.6
通讯作者：
Kornitzer D
中科院分区：
文献类型：
--
作者：
Ofir A;Hofmann K;Weindling E;Gildor T;Barker KS;Rogers PD;Kornitzer D
为了探索二相性真菌白色念珠菌的细胞周期调控，我们鉴定并鉴定了CaNrm1，它是酿酒酵母Whi5和Nrm1转录抑制物的白色念珠菌同源物，类似于哺乳动物Rb，在G1期调节细胞周期转录程序。CaNRM1能够补充酿酒酵母Whi5和nrm1突变体的表型。在白色念珠菌中，对CaNRM1缺失突变体的全局转录分析表明，优先诱导G1和G1/S特异性基因。CaNrm1与白念珠菌MBF功能同源物在基因上相互作用，在物理上与其亚单位CaSwi4相互作用。与酿酒酵母Whi5类似，CaNrm1的亚细胞定位随着细胞周期在细胞核和细胞质之间振荡。CaNRM1的缺失进一步导致了对DNA复制抑制物羟基脲的抵抗力增加；对羟基脲靶标核糖核苷酸还原酶的表达分析表明，其对羟基尿素的转录诱导是通过CaNrm1调节的，生化分析表明羟基尿素破坏了CaNrm1与CaSwi4的相互作用。此外，在某些条件下，Canrm1−/−突变体对菌丝特异基因的诱导受到抑制，这表明细胞周期转录程序可以影响白色念珠菌的形态发生转录程序。
To explore cell cycle regulation in the dimorphic fungus Candida albicans, we identified and characterized CaNrm1, a C. albicans homolog of the S. cerevisiae Whi5 and Nrm1 transcription inhibitors that, analogous to mammalian Rb, regulate the cell cycle transcription program during the G1 phase. CaNRM1 is able to complement the phenotypes of both whi5 and nrm1 mutants in S. cerevisiae. In C. albicans, global transcription analysis of the CaNRM1 deletion mutant reveals a preferential induction of G1 and G1/S-specific genes. CaNrm1 interacts genetically with the C. albicans MBF functional homolog, and physically with its subunit CaSwi4. Similar to S. cerevisiae Whi5, CaNrm1 subcellular localization oscillates with the cell cycle between the nucleus and the cytoplasm. Deletion of CaNRM1 further results in increased resistance to hydroxyurea, an inhibitor of DNA replication; analysis of the expression of ribonucleotide reductase, the target of hydroxyurea, suggests that its transcriptional induction in response to hydroxyurea is regulated via CaNrm1, and biochemical analysis shows that hydroxyurea causes disruption of the interaction of CaNrm1 with CaSwi4. Furthermore, induction of the hyphal-specific genes is dampened under certain conditions in the Canrm1−/− mutant, suggesting that the cell cycle transcription program can influence the morphogenetic transcription program of C. albicans.
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影响因子：
64.8
作者：
DIRICK, L;MOLL, T;NASMYTH, K
通讯作者：
NASMYTH, K
影响因子：
3.3
作者：
Bachewich, C;Thomas, DY;Whiteway, M
通讯作者：
Whiteway, M
影响因子：
16
作者：
de Bruin, Robertus A. M.;Kalashnikova, Tatyana I.;Wittenberg, Curt
通讯作者：
Wittenberg, Curt
影响因子：
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作者：
Hussein, Bahira;Huang, Hao;Bachewich, Catherine
通讯作者：
Bachewich, Catherine
影响因子：
3.3
作者：
Atir-Lande, A;Gildor, T;Kornitzer, D
通讯作者：
Kornitzer, D