The Minichromosome Maintenance Proteins 2-7 (MCM2-7) Are Necessary for RNA Polymerase II (Pol II)-mediated Transcription

Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York 10065, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 04/2009; 284(20):13466-72. DOI: 10.1074/jbc.M809471200
Source: PubMed


The MCM2-7 (minichromosome maintenance) proteins are a family of evolutionarily highly conserved proteins. They are essential for DNA replication in yeast and are considered to function as DNA helicases. However, it has long been shown that there is an overabundance of the MCM2-7 proteins when compared with the number of DNA replication origins in chromatin. It has been suggested that the MCM2-7 proteins may function in other biological processes that require the unwinding of the DNA helix. In this report, we show that RNA polymerase II (Pol II)-mediated transcription is dependent on MCM5 and MCM2 proteins. Furthermore, the MCM2-7 proteins are co-localized with RNA Pol II on chromatins of constitutively transcribing genes, and MCM5 is required for transcription elongation of RNA Pol II. Finally, we demonstrate that the integrity of the MCM2-7 hexamer complex and the DNA helicase domain in MCM5 are essential for the process of transcription.

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    • "MCM5 (minichromosome maintenance complex component 5) at 22q13.1 encodes for a member of the MCM family of chromatin-binding proteins that stimulates cell transition from G0 to G1/S phase of the cell cycle and actively participates in cell cycle regulation [22,23]. Data from clinical and preclinical models of skin, esophageal, bladder and gastrointestinal carcinomas further confirm the proliferative, migratory and cell cycle activating properties of the MCM5 protein [24-27]. "
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    • "E2F-1 and Rb protein, both of which regulate the expression of genes necessary for cell cycle progression and DNA replication [41], [42], also function at replication origins to limit DNA replication by interacting with proteins of the ORC, not by acting as transcription factors [43], [44]. Conversely, proteins involved in the assembly of pre-RC, viz., Mcm proteins 2–7, colocalize with RNA polymerase II on actively transcribing genes and are required for transcription elongation [45]. These interactions between transcription factors and proteins involved in the assembly of pre-RC may facilitate the orderly replication of transcriptionally active regions of genomic DNA in S phase. "
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    No preview · Article · Feb 2013 · PLoS ONE
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    • "Recent studies reported other replication proteins associated with protein-coding genes (Azvolinsky et al., 2009; Shor et al., 2009; Snyder et al., 2009), and some have argued this is a result of replisome pausing at sites of heavy transcription. However, we find RPA associating with transcription units even in G1 arrested cells (Figure S4B), indicating that the interaction with transcribed loci is replication independent. "
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