TRAIP/RNF206 is required for recruitment of RAP80 to sites of DNA damage

Lee, Nam Soo; Chung, Hee Jin; Kim, Hyoung-June; Lee, Seo Yun; Ji, Jeong‐Seon; Seo, Yeongeun; Han, Soon Woo; Choi, Minsu; Yun, Miyong; Lee, Seok‐Geun; Myung, Kyungjae; Kim, Yonghwan; Kang, Ho Chul; Kim, Hongtae

doi:10.1038/ncomms10463

Cited by 46 publications

(40 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The E3 ubiquitin ligase TRAIP counteracts replication stress to maintain genome integrity (Feng et al, 2016; Harley et al, 2016; Hoffmann et al, 2016; Soo Lee et al, 2016), and we recently found that it is bound to replication forks that have stalled at a LacR array (Dewar et al, 2017). We therefore asked whether TRAIP is responsible for CMG unloading from stalled forks in mitosis.…”

Section: Resultsmentioning

confidence: 99%

Mitotic CDK promotes replisome disassembly, fork breakage, and complex DNA rearrangements

Deng

Kochenova

et al. 2018

Preprint

View full text Add to dashboard Cite

22DNA replication errors generate complex chromosomal rearrangements and thereby 23 contribute to tumorigenesis and other human diseases. Although the events that trigger 24 these errors are not well understood, one candidate is mitotic entry before the 25 completion of DNA replication. To address the impact of mitosis on DNA replication, we 26 employed Xenopus egg extracts. When mitotic CDK (Cyclin B1-CDK1) is used to drive 27 these extracts into mitosis, the E3 ubiquitin ligase TRAIP promotes ubiquitylation of the 28 replicative CMG (CDC45/MCM2-7/GINS) helicase at stalled forks and at forks that have 29 completed DNA synthesis. In both cases, ubiquitylation is followed by CMG extraction 30 from chromatin by the CDC48/p97 ATPase. At stalled forks, CMG removal results in 31 fork breakage and complex end joining events involving deletions and template-32 switching. Our results identify TRAIP-dependent replisome disassembly as a novel 33 trigger of replication fork collapse and propose it underlies complex DNA 34 rearrangements in mitosis. 35 3 HIGHLIGHTS 36 1. TRAIP-dependent MCM7 ubiquitylation removes all CMGs from chromatin in 37 mitosis 38 2. CMG unloading from stalled forks causes replication fork breakage 39 3. Replication fork breakage in mitosis causes complex rearrangements 40 4. New model of replication fork collapse 41 42 43Genome evolution occurs through the gradual accrual of genetic changes or in a 44 saltatory manner, with bursts of chromosomal alterations originating from single 45 catastrophic events (Holland and Cleveland, 2012; Leibowitz et al., 2015; Liu et al., 46 2011; Stephens et al., 2011). Many chromosomal alterations can be traced to DNA 47 breaks that arise during DNA replication (Hills and Diffley, 2014; Mankouri et al., 2013; 48 Techer et al., 2017). However, there is an ongoing debate about when and how 49 replication fork breakage is triggered (Toledo et al., 2017). 50In normal cells, multiple cell cycle regulatory controls and error correction 51 mechanisms prevent DNA replication errors (Hills and Diffley, 2014). Cells prepare for 52 DNA replication in the G1 phase of the cell cycle, when pairs of MCM2-7 ATPases are 53 recruited to each origin ("licensing"). In S phase, cyclin-dependent kinase (CDK) 54 promotes the association of CDC45 and GINS with MCM2-7, leading to formation of the 55 replicative CMG helicase complex (CDC45-MCM2-7-GINS) ("initiation"). CMG 56 unwinding of the origin nucleates the assembly of two DNA replication forks that travel 57 away from the origin, copying DNA as they go ("elongation"). When converging forks 58 from adjacent origins meet, the replisome is disassembled ("termination"). Replisome 59 disassembly in S phase requires the E3 ubiquitin ligase CRL2 Lrr1 , which ubiquitylates 60 the MCM7 subunit of CMG, leading to CMG's extraction from chromatin by the p97 61 ATPase (Dewar et al., 2017; Sonneville et al., 2017). In the absence of CRL2 Lrr1 , CMGs 62 persist on chromatin until mitosis, but are then removed by a secondary, p97-dependent ...

show abstract

Section: Resultsmentioning

confidence: 99%

Mitotic CDK promotes replisome disassembly, fork breakage, and complex DNA rearrangements

Deng

Kochenova

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…Therefore, it can be said the localization of RAP80 is directly dependent on TRIP even in the absence of Deoxy-ribonucleic acid lesions. As such, it can be concluded that TRIP has a controlling function on RAP80 particularly in PML nuclear bodies [2]. The findings from the research revealed that TRIP transports RAP80 from PML nuclear bodies to the locus where the damage had occurred.…”

Section: Trip In Rap80 Signaling Pathwaymentioning

confidence: 77%

“…TRAF members directly interact with the TNFR super-family via their cytoplasmic domains [1]. Cytoplasmic domains of TNFR lack catalytic activity and possess no significant homology to each other or other known proteins [2]. To date, TRAF1-7 has been identified.…”

Section: Introductionmentioning

confidence: 99%

A TRIP Back in Time to TRIP

Bhat¹,

Rather²

2018

J Proteomics Bioinform

View full text Add to dashboard Cite

The studies report that TRIP is a negative factor in down-regulation of proinflammatory cytokine production through the TNF-induced NF-κB activation. More so, TRIP is used in pathways and processes like protein-protein interactions, TNF-induced signaling pathway, ubiquitination Assays, TNF-induced Signaling Pathway, TNFinduced p65 Nuclear Translocation Assay, Real-time PCR Analysis, Enzyme-linked Immunosorbent Assay (ELISA), Cytokine Expression Array, and Statistical Analysis. Furthermore, it acts as a regulator of TNF-induced inflammatory response. TRAF2 has a RING domain that participates in ligase activity. TRIP is also used in preventing Lys63-linked TRAF2 Ubiquitination through engagement of TNF receptor associated factor and TRAF-interacting protein. Similarly, TRIP destructively regulates ubiquitination mediated by TRAF-2. Additionally, it negatively affects TNF-induced NF-κB activation via the prevention of a RING domain in ligase. The research shows that TRAF-interacting protein is imperative in the activation through down-regulation of p65 phosphorylation. Moreover, TRIP is a factor in human disease and a sky-binding partner. Studies mention that TNF receptor-associated factor (TRAF)-interacting protein (TRIP) is a novel SyK-binding partner. Other than being a binding partner, TRIP is a factor in the pathogenesis of human diseases. TRIP-deficient mouse models have laid the basis to understand the roles of TRIP in the pathogenesis of human diseases. TRIP is also a key partner in DNA damage response. In fact, previous researches discovered that TRIP is found in DNA replication compartments particularly in DNA damage responses. Further studies show that TRIP also influences mitosis. According to Lee et al., TRIP acts as a novel binding agent of RAP80. It uses a yeast two-hybrid system. As such, it plays a critical role in the conscription of RAP80 to deoxy-ribonucleic acid lesions. Therefore, TRIP is a significant factor in different signaling processes and pathways.

show abstract

“…Consistent with this, a second pathway for RAP80 recruitment has recently been identified that is independent of RNF8/RNF168 ubiquitylation and SUMOylation. This pathway involves interactions between RAP80 and the protein TRAIP [35]. In response to DNA damage, TRAIP translocates to DSBs in complex with RAP80, where it interacts with the heterodimeric RNF20-RNF40 E3 complex.…”

Section: Rap80 Is Targeted To Dsbs Through Two Independent Pathwaysmentioning

confidence: 99%

“…As with RAP80 UIM and SIM mutant-expressing cells, RAP80 recruitment to DSBs is only partially inhibited in TRAIP-depleted cells. This suggests that optimal targeting and accumulation of RAP80 at DSBs is dependent on both TRAIP and ubiquitin and SUMO binding [35]. …”

Section: Rap80 Is Targeted To Dsbs Through Two Independent Pathwaysmentioning

confidence: 99%

RAP80, ubiquitin and SUMO in the DNA damage response

2017

View full text Add to dashboard Cite

A decade has passed since the first reported connection between RAP80 and BRCA1 in DNA double-strand break repair. Despite the initial identification of RAP80 as a factor localizing BRCA1 to DNA double-strand breaks and potentially promoting homologous recombination, there is increasing evidence that RAP80 instead suppresses homologous recombination to fine-tune the balance of competing DNA repair processes during the S/G2 phase of the cell cycle. RAP80 opposes homologous recombination by inhibiting DNA end-resection and sequestering BRCA1 into the BRCA1-A complex. Ubiquitin and SUMO modifications of chromatin at DNA double-strand breaks recruit RAP80, which contains distinct sequence motifs that recognize ubiquitin and SUMO. Here we review RAP80’s role in repressing homologous recombination at DNA double-strand breaks and how this role is facilitated by its ability to bind ubiquitin and SUMO modifications.

show abstract

TRAIP/RNF206 is required for recruitment of RAP80 to sites of DNA damage

Cited by 46 publications

References 33 publications

Mitotic CDK promotes replisome disassembly, fork breakage, and complex DNA rearrangements

Mitotic CDK promotes replisome disassembly, fork breakage, and complex DNA rearrangements

A TRIP Back in Time to TRIP

RAP80, ubiquitin and SUMO in the DNA damage response

Contact Info

Product

Resources

About