Temporal profile of replication of human chromosomes
Temporal profile of replication of human chromosomes
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DOI：
10.1073/pnas.0405088102
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发表时间：
2005-05-03
影响因子：
11.1
通讯作者：
Dutta, A
中科院分区：
文献类型：
--
作者：
Jeon, Y;Bekiranov, S;Dutta, A
人类癌细胞中的染色体预计会从可预测的局部起点开始复制，在 S 期的离散时间重复激发。从 S 期不同阶段的 HeLa 细胞获得的复制产物与 cDNA 和基因组平铺寡核苷酸微阵列杂交，以确定人类染色体在全基因组范围内复制的时间概况。大约 1,000 个基因和染色体片段被鉴定为含有可重复激发的有效起源的位点。早期复制与高基因密度相关。基因密度从早期复制区域到晚期复制区域的急剧转变表明离散的染色质状态决定早期复制与晚期复制。令人惊讶的是，至少 60% 的受检染色体片段在 S 期的所有部分均等地复制，这表明大片染色体是通过低效、位置可变且异步的起点和分叉进行复制的，从而产生了泛 S 期复制模式。因此，至少对于非整倍体癌细胞来说，对于大段染色体来说，没有看到典型的 S 期离散复制时间。
Chromosomes in human cancer cells are expected to initiate replication from predictably localized origins, firing reproducibly at discrete times in S phase. Replication products obtained from HeLa cells at different stages of S phase were hybridized to cDNA and genome tiling oligonucleoticle microarrays to determine the temporal profile of replication of human chromosomes on a genome-wide scale. About 1,000 genes and chromosomal segments were identified as sites containing efficient origins that fire reproducibly. Early replication was correlated with high gene density. An acute transition of gene density from early to late replicating areas suggests that discrete chromatin states dictate early versus late replication. Surprisingly, at least 60% of the interrogated chromosomal segments replicate equally in all quarters of S phase, suggesting that large stretches of chromosomes are replicated by inefficient, variably located and asynchronous origins and forks, producing a pan-S phase pattern of replication. Thus, at least for aneuploid cancer cells, a typical discrete time of replication in S phase is not seen for large segments of the chromosomes.