Abstract：
:Here we demonstrate that RNF4, a highly conserved small ubiquitin-like modifier (SUMO)-targeted ubiquitin E3 ligase, plays a critical role in the response of mammalian cells to DNA damage. Human cells in which RNF4 expression was ablated by siRNA or chicken DT40 cells with a homozygous deletion of the RNF4 gene displayed increased sensitivity to DNA-damaging agents. Recruitment of RNF4 to double-strand breaks required its RING and SUMO interaction motif (SIM) domains and DNA damage factors such as NBS1, mediator of DNA damage checkpoint 1 (MDC1), RNF8, 53BP1, and BRCA1. In the absence of RNF4, these factors were still recruited to sites of DNA damage, but 53BP1, RNF8, and RNF168 displayed delayed clearance from such foci. SILAC-based proteomics of SUMO substrates revealed that MDC1 was SUMO-modified in response to ionizing radiation. As a consequence of SUMO modification, MDC1 recruited RNF4, which mediated ubiquitylation at the DNA damage site. Failure to recruit RNF4 resulted in defective loading of replication protein A (RPA) and Rad51 onto ssDNA. This appeared to be a consequence of reduced recruitment of the CtIP nuclease, resulting in inefficient end resection. Thus, RNF4 is a novel DNA damage-responsive protein that plays a role in homologous recombination and integrates SUMO modification and ubiquitin signaling in the cellular response to genotoxic stress.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Yin Y,Seifert A,Chua JS,Maure JF,Golebiowski F,Hay RTdoi
10.1101/gad.189274.112subject
Has Abstractpub_date
2012-06-01 00:00:00pages
1196-208issue
11eissn
0890-9369issn
1549-5477pii
26/11/1196journal_volume
26pub_type
杂志文章abstract：:In the July 15, 2010, issue of Genes & Development, Yoon and colleagues (pp. 1507-1518) report that, in a siRNA knockdown survey of 6363 genes in mouse C2C12 cells, they discovered 150 genes that regulated mitochondrial biogenesis and bioenergetics. Many of these genes have been studied previously for their importance...
journal_title：Genes & development
pub_type： 评论,杂志文章
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abstract：:In the yeast Saccharomyces cerevisiae, sequence-specific DNA binding by the origin recognition complex (ORC) is responsible for selecting origins of DNA replication. In metazoans, origin selection is poorly understood and it is unknown whether specific DNA binding by metazoan ORC controls replication. To address this ...
journal_title：Genes & development
pub_type： 杂志文章
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journal_title：Genes & development
pub_type： 杂志文章
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journal_title：Genes & development
pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Genes & development
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pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Genes & development
pub_type： 杂志文章
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journal_title：Genes & development
pub_type： 杂志文章
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journal_title：Genes & development
pub_type： 评论,杂志文章
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更新日期：2011-11-15 00:00:00
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journal_title：Genes & development
pub_type： 杂志文章
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更新日期：1992-08-01 00:00:00
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journal_title：Genes & development
pub_type： 评论,杂志文章
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journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.398207
更新日期：2007-02-01 00:00:00
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journal_title：Genes & development
pub_type： 评论,杂志文章,评审
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更新日期：2009-12-15 00:00:00
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journal_title：Genes & development
pub_type： 杂志文章
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更新日期：2012-09-15 00:00:00
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journal_title：Genes & development
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journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.6.10.1927
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pub_type： 杂志文章
doi：10.1101/gad.2.11.1424
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pub_type： 评论
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journal_title：Genes & development
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journal_title：Genes & development
pub_type： 杂志文章
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journal_title：Genes & development
pub_type： 杂志文章
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更新日期：2008-01-15 00:00:00
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journal_title：Genes & development
pub_type： 杂志文章
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journal_title：Genes & development
pub_type： 杂志文章
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更新日期：1996-03-01 00:00:00
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journal_title：Genes & development
pub_type： 杂志文章
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更新日期：2006-10-15 00:00:00
abstract：:Chromosome replication occurs precisely once during the cell cycle of almost all eukaryotic cells, and is a highly complex process that is still understood relatively poorly. Two conserved kinases called Cdc7 (cell division cycle 7) and cyclin-dependent kinase (CDK) are required to establish replication forks during t...
journal_title：Genes & development
pub_type： 杂志文章,评审
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更新日期：2010-06-15 00:00:00
abstract：:The tobacco mitogen-activated protein kinase (MAPK) cascade, which includes MAPK NRK1/NTF6, positively regulates expansion of the cytokinetic machinery known as the phragmoplast, which is followed by the synthesis of cell plates for completion of cell division. However, molecular events lying between the MAPK and phra...
journal_title：Genes & development
pub_type： 杂志文章
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更新日期：2006-04-15 00:00:00
