BLM Sumoylation Is Required for Replication Stability and Normal Fork Velocity During DNA Replication.
BLM Sumoylation Is Required for Replication Stability and Normal Fork Velocity During DNA Replication.
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DOI：
10.3389/fmolb.2022.875102
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发表时间：
2022
影响因子：
5
通讯作者：
中科院分区：
文献类型：
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BLM在复制应激反应中被sumoylated。我们已经研究了BLM类小泛素化在生理正常和复制应激条件下的作用，通过在BLM缺陷细胞中表达具有SUMO受体位点突变的BLM，我们将其称为SUMO突变BLM细胞。SUMO突变体BLM细胞表现出多重缺陷，在强调和未强调的DNA复制条件下，包括，在羟基脲处理的细胞，减少叉重新启动和增加叉崩溃，并在未经处理的细胞，较慢的叉速度和增加叉不稳定性的测定轨道长度不对称。我们进一步通过光漂白后的荧光恢复表明，SUMO突变BLM蛋白的动态性低于正常BLM，并且在复制叉折叠时包含更高的不动部分。BLM类小泛素化先前已被链接到招聘的RAD 51强调叉在羟基脲处理的细胞。一个重要的未解决的问题是，是否未能有效地招募RAD 51是在未经处理的SUMO突变BLM细胞的复制应力的解释。
BLM is sumoylated in response to replication stress. We have studied the role of BLM sumoylation in physiologically normal and replication-stressed conditions by expressing in BLM-deficient cells a BLM with SUMO acceptor-site mutations, which we refer to as SUMO-mutant BLM cells. SUMO-mutant BLM cells exhibited multiple defects in both stressed and unstressed DNA replication conditions, including, in hydroxyurea-treated cells, reduced fork restart and increased fork collapse and, in untreated cells, slower fork velocity and increased fork instability as assayed by track-length asymmetry. We further showed by fluorescence recovery after photobleaching that SUMO-mutant BLM protein was less dynamic than normal BLM and comprised a higher immobile fraction at collapsed replication forks. BLM sumoylation has previously been linked to the recruitment of RAD51 to stressed forks in hydroxyurea-treated cells. An important unresolved question is whether the failure to efficiently recruit RAD51 is the explanation for replication stress in untreated SUMO-mutant BLM cells.
DOI：
10.1083/jcb.200402095
发表时间：
2004-06-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Li W;Kim SM;Lee J;Dunphy WG
通讯作者：
Dunphy WG