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秀丽隐杆线虫的指环蛋白 RNF-113 参与链间 DNA 交联修复，并与 RAD51C 同源物相互作用。

C. elegans ring finger protein RNF-113 is involved in interstrand DNA crosslink repair and interacts with a RAD51C homolog.

机构信息

Department of Biochemistry, College of Life Science & Biotechnology, Yonsei University, Seoul, Republic of Korea.

出版信息

PLoS One. 2013;8(3):e60071. doi: 10.1371/journal.pone.0060071. Epub 2013 Mar 28.

DOI:10.1371/journal.pone.0060071
PMID:23555887
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3610817/
Abstract

The Fanconi anemia (FA) pathway recognizes interstrand DNA crosslinks (ICLs) and contributes to their conversion into double-strand DNA breaks, which can be repaired by homologous recombination. Seven orthologs of the 15 proteins associated with Fanconi anemia are functionally conserved in the model organism C. elegans. Here we report that RNF-113, a ubiquitin ligase, is required for RAD-51 focus formation after inducing ICLs in C. elegans. However, the formation of foci of RPA-1 or FCD-2/FANCD2 in the FA pathway was not affected by depletion of RNF-113. Nevertheless, the RPA-1 foci formed did not disappear with time in the depleted worms, implying serious defects in ICL repair. As a result, RNF-113 depletion increased embryonic lethality after ICL treatment in wild-type worms, but it did not increase the ICL-induced lethality of rfs-1/rad51C mutants. In addition, the persistence of RPA-1 foci was suppressed in doubly-deficient rnf-113;rfs-1 worms, suggesting that there is an epistatic interaction between the two genes. These results lead us to suggest that RNF-113 and RFS-1 interact to promote the displacement of RPA-1 by RAD-51 on single-stranded DNA derived from ICLs.

摘要

范可尼贫血（FA）途径识别链间 DNA 交联（ICLs），并有助于将其转化为双链 DNA 断裂，这些断裂可以通过同源重组修复。与范可尼贫血相关的 15 种蛋白质的 7 个同源物在模式生物秀丽隐杆线虫中具有功能保守性。在这里，我们报告说，泛素连接酶 RNF-113 在诱导秀丽隐杆线虫中的 ICL 后，RAD-51 焦点的形成是必需的。然而，RNF-113 耗竭并不影响 FA 途径中 RPA-1 或 FCD-2/FANCD2 焦点的形成。尽管如此，在耗竭的线虫中，形成的 RPA-1 焦点不会随时间消失，这意味着 ICL 修复存在严重缺陷。因此，RNF-113 耗竭增加了野生型线虫中 ICL 处理后的胚胎致死率，但不会增加 rfs-1/rad51C 突变体中 ICL 诱导的致死率。此外，在 rnf-113; rfs-1 双缺失线虫中，RPA-1 焦点的持续存在受到抑制，这表明这两个基因之间存在上位性相互作用。这些结果使我们提出，RNF-113 和 RFS-1 相互作用，以促进 RAD-51 取代源自 ICL 的单链 DNA 上的 RPA-1。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf37/3610817/3af6d8807cfa/pone.0060071.g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf37/3610817/3af6d8807cfa/pone.0060071.g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf37/3610817/fa070623abac/pone.0060071.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf37/3610817/7315173dc3a3/pone.0060071.g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf37/3610817/3af6d8807cfa/pone.0060071.g006.jpg

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