Nuclear reorganization of mammalian DNA synthesis prior to cell cycle exit
Nuclear reorganization of mammalian DNA synthesis prior to cell cycle exit
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DOI：
10.1128/mcb.24.2.595-607.2004
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发表时间：
2004-01-01
影响因子：
5.3
通讯作者：
Kennedy, BK
中科院分区：
文献类型：
--
作者：
Barbie, DA;Kudlow, BA;Kennedy, BK
在原代哺乳动物细胞中，DNA复制起始于少量的核仁周核纤层蛋白A/C相关灶。在增殖细胞的S期进程中，复制灶分布于整个细胞核的数百个位点。相比之下，我们发现，有限的perinucleolar复制位点持续整个S期细胞准备退出细胞周期的接触抑制，血清饥饿，或复制衰老。已知参与DNA合成的蛋白质，如PCNA和DNA聚合酶δ，在这些条件下在整个S期集中在核仁周围病灶。此外，染色体基因座被重定向到核仁，并与准备经历细胞周期退出的细胞中的核仁周复制灶重叠。在高度增殖条件下复制期间，这些相同的位点保留在细胞核的外周。这些结果表明，哺乳动物细胞在细胞周期退出之前的DNA复制轮次期间经历了大规模的染色质重组。
In primary mammalian cells, DNA replication initiates in a small number of perinucleolar, lamin A/C-associated foci. During S-phase progression in proliferating cells, replication foci distribute to hundreds of sites throughout the nucleus. In contrast, we find that the limited perinucleolar replication sites persist throughout S phase as cells prepare to exit the cell cycle in response to contact inhibition, serum starvation, or replicative senescence. Proteins known to be involved in DNA synthesis, such as PCNA and DNA polymerase delta, are concentrated in perinucleolar foci throughout S phase under these conditions. Moreover, chromosomal loci are redirected toward the nucleolus and overlap with the perinucleolar replication foci in cells poised to undergo cell cycle exit. These same loci remain in the periphery of the nucleus during replication under highly proliferative conditions. These results suggest that mammalian cells undergo a large-scale reorganization of chromatin during the rounds of DNA replication that precede cell cycle exit.