DNA复制因子CDT1
生物
染色体复制控制
DNA复制
原点识别复合体
复制前复合体
许可因素
DNA再复制
细胞生物学
真核细胞DNA复制
DNA合成
解旋酶
微小染色体维持
泛素连接酶
复制因子C
复制的起源
DNA
遗传学
泛素
基因
核糖核酸
作者
Nalin Ratnayeke,Yasemin Baris,Mingyu Chung,Joseph T P Yeeles,Tobias Meyer
出处
期刊:Molecular Cell
[Elsevier]
日期:2023-01-01
卷期号:83 (1): 26-42.e13
被引量:2
标识
DOI:10.1016/j.molcel.2022.12.004
摘要
Human cells license tens of thousands of origins of replication in G1 and then must stop all licensing before DNA synthesis in S phase to prevent re-replication and genome instability that ensue when an origin is licensed on replicated DNA. However, the E3 ubiquitin ligase CRL4Cdt2 only starts to degrade the licensing factor CDT1 after origin firing, raising the question of how cells prevent re-replication before CDT1 is fully degraded. Here, using quantitative microscopy and in-vitro-reconstituted human DNA replication, we show that CDT1 inhibits DNA synthesis during an overlap period when CDT1 is still present after origin firing. CDT1 inhibits DNA synthesis by suppressing CMG helicase at replication forks, and DNA synthesis commences once CDT1 is degraded. Thus, in contrast to the prevailing model that human cells prevent re-replication by strictly separating licensing from firing, licensing and firing overlap, and cells instead separate licensing from DNA synthesis.
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