SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase
SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase
复制标题
DOI：
10.1038/nature03665
复制
发表时间：
2005-07-21
期刊：
影响因子：
64.8
通讯作者：
Jentsch, S
中科院分区：
文献类型：
--
作者：
Pfander, B;Moldovan, GL;Jentsch, S
受损的DNA，如果在复制前没有修复，可能会导致复制叉停滞和基因组不稳定（1-3）;然而，细胞可以切换到不同的损伤旁路模式，允许跨病变复制。两个主要旁路由增殖细胞核抗原（PCNA）的泛素修饰控制，PCNA是一种同源三聚体DNA环绕蛋白，作为聚合酶合成因子和复制相关功能的调节因子（4，5）。在DNA损伤后，PCNA在保守的赖氨酸残基164处被单泛素或赖氨酸-63连接的多泛素链修饰（5），其诱导病变的易错或无错复制绕过（5，6）。在S期，即使在没有外源DNA损伤的情况下，酵母PCNA也可以被小的泛素相关修饰蛋白SUMO 5替代地修饰;然而，其结果仍然存在争议（5-7）。在这里，我们通过遗传分析表明SUMO修饰的PCNA在功能上与Srs 2合作，Srs 2是一种解旋酶，通过破坏Rad 51核蛋白丝来阻断重组修复（8，9）。此外，Srs 2显示直接与SUMO修饰形式的PCNA相互作用的偏好，由于其羧基末端尾部的特异性结合位点。我们的发现表明，SUMO修饰的PCNA在S期招募Srs 2，以防止复制染色体的不必要的重组事件的模型。
Damaged DNA, if not repaired before replication, can lead to replication fork stalling and genomic instability(1-3); however, cells can switch to different damage bypass modes that permit replication across lesions. Two main bypasses are controlled by ubiquitin modification of proliferating cell nuclear antigen ( PCNA), a homotrimeric DNA-encircling protein that functions as a polymerase processivity factor and regulator of replication-linked functions(4,5). Upon DNA damage, PCNA is modified at the conserved lysine residue 164 by either mono-ubiquitin or a lysine-63-linked multi-ubiquitin chain(5), which induce error-prone or error-free replication bypasses of the lesions(5,6). In S phase, even in the absence of exogenous DNA damage, yeast PCNA can be alternatively modified by the small ubiquitin-related modifier protein SUMO5; however the consequences of this remain controversial(5-7). Here we show by genetic analysis that SUMO-modified PCNA functionally cooperates with Srs2, a helicase that blocks recombinational repair by disrupting Rad51 nucleoprotein filaments(8,9). Moreover, Srs2 displays a preference for interacting directly with the SUMO-modified form of PCNA, owing to a specific binding site in its carboxy-terminal tail. Our finding suggests a model in which SUMO-modified PCNA recruits Srs2 in S phase in order to prevent unwanted recombination events of replicating chromosomes.