Break-induced replication requires all essential DNA replication factors except those specific for pre-RC assembly
Break-induced replication requires all essential DNA replication factors except those specific for pre-RC assembly
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DOI：
10.1101/gad.1922610
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发表时间：
2010-06-01
影响因子：
10.5
通讯作者：
Haber, James E.
中科院分区：
文献类型：
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作者：
Lydeard, John R.;Lipkin-Moore, Zachary;Haber, James E.
断裂诱导复制（BIR）是一种有效的同源重组（HR）途径，用于修复同源性局限于一端的DNA双链断裂（DSB）。所有三种主要的复制DNA聚合酶都是BIR所必需的，包括其他非必需的Pol32亚基。在这里，我们发现BIR需要复制DNA解旋酶（Cdc45、GINS和Mcm2-7蛋白）和Cdt1。相比之下，起源识别复合体（ORC）和Cdc6亚基都是可缺性的，它们是产生预复制复合体（pre-RC）所必需的。DNA复制起始和复制后修复（PRR）都需要Cdc7激酶，BIR也需要Cdc7激酶。DNA加工钳制PCNA的泛素化和聚合化发挥适度的作用；相比之下，抑制pol32 Delta冷敏感性的PCNA等位基因不能抑制其在BIR中的作用，并且它们本身是BIR的显性抑制剂。这些结果表明，起源无关的BIR涉及正常DNA复制因子和PRR之间的串扰。
Break-induced replication (BIR) is an efficient homologous recombination (HR) pathway employed to repair a DNA double-strand break (DSB) when homology is restricted to one end. All three major replicative DNA polymerases are required for BIR, including the otherwise nonessential Pol32 subunit. Here we show that BIR requires the replicative DNA helicase (Cdc45, the GINS, and Mcm2-7 proteins) as well as Cdt1. In contrast, both subunits of origin recognition complex (ORC) and Cdc6, which are required to create a prereplication complex (pre-RC), are dispensable. The Cdc7 kinase, required for both initiation of DNA replication and post-replication repair (PRR), is also required for BIR. Ubiquitination and sumoylation of the DNA processivity clamp PCNA play modest roles; in contrast, PCNA alleles that suppress pol32 Delta's cold sensitivity fail to suppress its role in BIR, and are by themselves dominant inhibitors of BIR. These results suggest that origin-independent BIR involves cross-talk between normal DNA replication factors and PRR.