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PCNA is monoubiquitylated during replication of undamaged DNA in frog eggs, report Leach and Michael on page 947, and preventing the modification slows fork progression. Thus, cells may have a mechanism for modulating the speed of replication, an idea that runs counter to long-standing dogma.
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Homotrimers of unmodified PCNA clamp onto DNA during replication and increase the processivity of polymerase , which is the workhorse of normal replication. In response to DNA damage, PCNA is monoubiquitylated in mammalian cells and mono- and polyubiquitylated in yeast. The modified protein assists in recruitment of polymerase to sites of damage.
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Leach and Michael found that Xenopus PCNA was monoubiquitylated or sumoylated during replication of undamaged DNA in egg extracts. The protein was polyubiquitylated in the presence of damaged DNA. Sumoylation was not required for replication, though inhibition of PCNA ubiquitylation slowed fork progression. Replication forks were not abandoned more frequently in the absence of ubiquitylation than in control cells.5 k7 V; _- M- ^7 Z9 o. S( k
7 ^) ^6 p. H3 wWhen the polymerase slowed, the helicase also slowed, which suggests that the cells have a system in place to compensate for changes in the rate of fork movement.
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The differences found in PCNA modifications in frog and mammalian cells could indicate that such regulatory changes are not conserved between species. Alternatively, the observations could reflect differences between embryonic DNA replication, which was studied here, and somatic cell replication, which was studied previously in mammalian cells.
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Until now, it was thought that an increase in the number of forks fired was sufficient to account for the greater replication rate in embryonic cells relative to somatic cells. But the regulation observed here is one additional candidate for determining this difference in speed.(PCNA that can't be ubiquitylated (right)) |
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发表于 2009-3-6 09:04
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