Tsolou Avgi, Lydall David
Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Henry Wellcome Laboratory for Biogerontology Research, Newcastle University, Newcastle upon Tyne NE4 6BE, UK.
DNA Repair (Amst). 2007 Nov;6(11):1607-17. doi: 10.1016/j.dnarep.2007.05.010. Epub 2007 Jul 6.
Mrc1 (Mediator of Replication Checkpoint 1) is a component of the DNA replication fork machinery and is necessary for checkpoint activation after replication stress. In this study, we addressed the role of Mrc1 at uncapped telomeres. Our experiments show that Mrc1 contributes to the vitality of both cdc13-1 and yku70Delta telomere capping mutants. Cells with telomere capping defects containing MRC1 or mrc1(AQ), a checkpoint defective allele, exhibit similar growth, suggesting growth defects of cdc13-1 mrc1Delta are not due to checkpoint defects. This is in accordance with Mrc1-independent Rad53 activation after telomere uncapping. Poor growth of cdc13-1 mutants in the absence of Mrc1 is a result of enhanced single stranded DNA accumulation at uncapped telomeres. Consistent with this, deletion of EXO1, encoding a nuclease that contributes to single stranded DNA accumulation after telomere uncapping, improves growth of cdc13-1 mrc1Delta strains and decreases ssDNA production. Our observations show that Mrc1, a core component of the replication fork, plays an important role in telomere capping, protecting from nucleases and checkpoint pathways.
Mrc1（复制检查点1介导因子）是DNA复制叉机制的一个组成部分，在复制应激后激活检查点时是必需的。在本研究中，我们探讨了Mrc1在无帽端粒中的作用。我们的实验表明，Mrc1对cdc13-1和yku70Delta端粒封端突变体的活力都有贡献。含有MRC1或mrc1（AQ）（一种检查点缺陷等位基因）的端粒封端缺陷细胞表现出相似的生长情况，这表明cdc13-1 mrc1Delta的生长缺陷并非由于检查点缺陷。这与端粒去帽后不依赖Mrc1的Rad53激活一致。在没有Mrc1的情况下，cdc13-1突变体生长不良是无帽端粒上单链DNA积累增加的结果。与此一致的是，编码一种在端粒去帽后有助于单链DNA积累的核酸酶Exo1的缺失，改善了cdc13-1 mrc1Delta菌株的生长并减少了单链DNA的产生。我们的观察结果表明，复制叉的核心组成部分Mrc1在端粒封端中起重要作用，可保护免受核酸酶和检查点途径的影响。
