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Cmg Helicase. First the minichromosome maintenance MCM complex assembles as a head-to-head double hexamer that encircles duplex replication origin DNA during G1 phase. CMG contains the ring-shaped hexameric Mcm27 that harbors the helicase motors. The mechanism of eukaryotic CMG helicase activation. Little is known about how CMG is dismantled from chromatin both when replication forks meet during termination and in response to certain forms of replication stress.
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Therefore it is difficult to envision a clinical situation where tumors can circumvent the CMG helicase and a CMGi by using an alternative enzyme or pathway. Multiple factors associate directly with CMG including Ctf4 and the heterotrimeric fork protection complex Csm3Tof1 and Mrc1 which has important roles including aiding normal replication rates and stabilizing stalled forks. The eukaryotic replisome is disassembled in each cell cycle dependent upon ubiquitylation of the CMG helicase. Langston LD Zhang D Yurieva O Georgescu RE Finkelstein J Yao NY Indiani C ODonnell ME. The CMG helicase was isolated by immunoprecipitation of Sld5 before immunoblotting and detection of Cy3 fluorescence. Replicative helicase CMG bypasses DNA-protein crosslinks on its translocation strand RTEL1 an accessory helicase facilitates bypass by unwinding DNA beyond the DPC CMG slows after bypass likely due to uncoupling from DNA synthesis.
The eukaryotic replicative helicase CMG is a closed ring around double-stranded dsDNA at origins yet must transition to single-stranded ssDNA for helicase action.
The CMG Helicase Bypasses DNA-Protein Cross-Links to Facilitate Their Repair Graphical Abstract Highlights d Replicative helicase CMG bypasses DNA-protein crosslinks on its translocation strand d RTEL1 an accessory helicase facilitates bypass by unwinding DNA beyond the DPC d CMG slows after bypass likely due to uncoupling from DNA synthesis. Recombinant CMG helicase was mixed with Cy3-labelled versions of the DNA substrates shown in Figure 2C i and then incubated for 60 min on ice. These annotations have been derived from physical molecular interaction evidence extracted from the literature and cross-referenced in the entry or by curator inference from information on homologs in closely related species or by inference from scientific background. Therefore it is difficult to envision a clinical situation where tumors can circumvent the CMG helicase and a CMGi by using an alternative enzyme or pathway. The CMG Cdc45-MCM-GINS helicase surrounds the leading strand and is proposed to recruit Pol ε for leading-strand synthesis but to date a direct interaction between CMG and Pol ε has not been demonstrated. This CMG helicase is important for DNA replication and recovering from fork-stalling chemotherapy.
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Therefore it is difficult to envision a clinical situation where tumors can circumvent the CMG helicase and a CMGi by using an alternative enzyme or pathway. Studies of Saccharomyces cerevisiae Caenorhabditis elegans and Xenopus laevis have revealed surprising evolutionary diversity in the ubiquitin ligases that control CMG ubiquitylation but regulated disassembly of the mammalian replisome has yet to be explored. From this point onwards each CMG helicase moves along a single parental DNA strand that is no longer connected to the other. CMG helicase and DNA polymerase epsilon form a functional 15-subunit holoenzyme for eukaryotic leading-strand DNA replication. These annotations have been derived from physical molecular interaction evidence extracted from the literature and cross-referenced in the entry or by curator inference from information on homologs in closely related species or by inference from scientific background.
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First the minichromosome maintenance MCM complex assembles as a head-to-head double hexamer that encircles duplex replication origin DNA during G1 phase. The eukaryotic replisome organized around the Cdc45-MCM-GINS CMG helicase orchestrates chromosome replication. Thus the threading of DNA through the CMG helicase at a replication fork determines the. CMG must also handle repair intermediates such as reversed forks that lack ssDNA. After activation the two CMG helicases translocate in an N terminus-first direction and in doing so pass each other within the origin.
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