Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae

Ostrow A. Zachary; Kalhor Reza; Gan YanVillwock Sandra K.Linke ChristianBarberis MatteoChen LinAparicio Oscar M.

首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America. >Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae

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Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae

机译：Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae

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Forkhead Box (Fox) proteins share the Forkhead domain, a winged-helix DNA binding module, which is conserved among eukaryotes from yeast to humans. These sequence-specific DNA binding proteins have been primarily characterized as transcription factors regulating diverse cellular processes from cell cycle control to developmental fate, deregulation of which contributes to developmental defects, cancer, and aging. We recently identified Saccharomyces cerevisiae Forkhead 1 (Fkh1) and Forkhead 2 (Fkh2) as required for the clustering of a subset of replication origins in G(1) phase and for the early initiation of these origins in the ensuing S phase, suggesting a mechanistic role linking the spatial organization of the origins and their activity. Here, we show that Fkh1 and Fkh2 share a unique structural feature of human FoxP proteins that enables FoxP2 and FoxP3 to form domain-swapped dimers capable of bridging two DNA molecules in vitro. Accordingly, Fkh1 self-associates in vitro and in vivo in a manner dependent on the conserved domain-swapping region, strongly suggestive of homodimer formation. Fkh1-and Fkh2-domain-swap-minus (dsm) mutations are functional as transcription factors yet are defective in replication origin timing control. Fkh1-dsm binds replication origins in vivo but fails to cluster them, supporting the conclusion that Fkh1 and Fkh2 dimers perform a structural role in the spatial organization of chromosomal elements with functional importance.

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《Proceedings of the National Academy of Sciences of the United States of America.》 |2017年第12期|E2411-E2419|共9页
作者
Ostrow A. Zachary; Kalhor Reza; Gan YanVillwock Sandra K.Linke ChristianBarberis MatteoChen LinAparicio Oscar M.;
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作者单位

Univ Southern Calif, Mol & Computat Biol Program, Los Angeles, CA 90089 USA;

Univ Amsterdam, Swammerdam Inst Life Sci, Synthet Syst Biol & Nucl Org, NL-1098 XH Amsterdam, Netherlands;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
DNA replication timing; chromatin; nuclear organization; Fox proteins; DNA binding protein;

Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae

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