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Article
The ATM–Chk2–Cdc25A checkpoint pathway guards against radioresistant DNA synthesis
When exposed to ionizing radiation (IR), eukaryotic cells activate checkpoint pathways to delay the progression of the cell cycle1,2,3. Defects in the IR-induced S-phase checkpoint cause ‘radioresistant DNA synth...
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Article
Deregulated human Cdc14A phosphatase disrupts centrosome separation and chromosome segregation
We show that human Cdc14A phosphatase1 interacts with interphase centrosomes, and that this interaction is independent of microtubules and Cdc14A phosphatase activity, but requires active nuclear export. Disrupti...
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Article
Centrosome-associated Chk1 prevents premature activation of cyclin-B–Cdk1 kinase
Entry into mitosis occurs after activation of Cdk1, resulting in chromosome condensation in the nucleus and centrosome separation, as well as increased microtubule nucleation activity in the cytoplasm. The act...
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Article
HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes
HERC2 regulates the retention of repair proteins 53BP1, RAP80 and BRCA1 on damaged chromosomes in response to ionizing radiation by forming a complex with the ubiquitin ligases RNF8 and RNF168. Hecr2 deficienc...
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Article
Erratum: HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes
Nature Cell Biol. 12, 80–81 (2010); published online 20 December 2009; corrected after print, 10 March 2010 In the version of this Letter initially published, an author, Claudia Lukas, was omitted. The author ...
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Article
The ubiquitin-selective segregase VCP/p97 orchestrates the response to DNA double-strand breaks
The p97 AAA+ ATPase (also known as VCP) functions in various ubiquitin-regulated processes. Ramadan and colleagues now find that p97 is recruited to sites of DNA damage by Lys-48-linked ubiquitin chains, which...
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Article
ICLs: a chicken without an egg
Two studies identify aldehyde metabolites as a potential endogenous source of ICLs.
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Article
Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass
Protein ubiquitylation has emerged as a key regulatory mechanism in DNA-damage signalling and repair pathways. We report a proteome-wide, site-specific survey of ubiquitylation changes after ultraviolet irradi...
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Article
DVC1 (C1orf124) is a DNA damage–targeting p97 adaptor that promotes ubiquitin-dependent responses to replication blocks
The AAA ATPase p97 (VCP) is thought to remove specific proteins from chromatin at sites of DNA damage, to allow proper repair or processing, but how p97 targets those sites was unclear. The protein DVC1 is now...
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Article
Regulation of PCNA–protein interactions for genome stability
The sliding clamp proliferating cell nuclear antigen (PCNA) has a crucial role as a processivity factor for DNA replication in eukaryotic cells. PCNA provides ...
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Article
Open AccessAgo2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination
DNA double-strand breaks (DSBs) are highly cytotoxic lesions and pose a major threat to genome stability if not properly repaired. We and others have previously shown that a class of DSB-induced small RNAs (di...
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Article
Centriolar satellites: key mediators of centrosome functions
Centriolar satellites are small, microscopically visible granules that cluster around centrosomes. These structures, which contain numerous proteins directly involved in centrosome maintenance, ciliogenesis, a...
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Article
Open AccessSUMO and ubiquitin-dependent XPC exchange drives nucleotide excision repair
XPC recognizes UV-induced DNA lesions and initiates their removal by nucleotide excision repair (NER). Damage recognition in NER is tightly controlled by ubiquitin and SUMO modifications. Recent studies have s...
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Article
RNF138 joins the HR team
Two studies show that the E3 ubiquitin ligase RNF138 is recruited to DNA double-strand break sites, where it ubiquitylates key repair factors to promote DNA-end resection and homologous recombination. These fi...
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Article
Histone H1 couples initiation and amplification of ubiquitin signalling after DNA damage
At the initiation of DNA double-strand break repair, a number of ubiquitylation events occur; here, the RNF8 ubiquitin E3 ligase and the ubiquitin-conjugating E2 enzyme, UBC13, are shown to primarily modify H1...
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Article
Open Accessp38- and MK2-dependent signalling promotes stress-induced centriolar satellite remodelling via 14-3-3-dependent sequestration of CEP131/AZI1
Centriolar satellites (CS) are small granular structures that cluster in the vicinity of centrosomes. CS are highly susceptible to stress stimuli, triggering abrupt displacement of key CS factors. Here we disc...
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Article
H4K20me0 marks post-replicative chromatin and recruits the TONSL–MMS22L DNA repair complex
We have a limited understanding of how cells mark and identify newly replicated genomic loci that have a sister chromatid; here, unmethylated K20 in the tail of new histone H4 is shown to serve as a signature ...
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Article
Regulation of DNA double-strand break repair by ubiquitin and ubiquitin-like modifiers
Post-translational modification of proteins by ubiquitin and ubiquitin-like modifiers (UBLs) including SUMO have crucial and widespread roles in promoting cell...
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Article
Activation of the ATR kinase by the RPA-binding protein ETAA1
Activation of the ATR kinase following perturbations to DNA replication relies on a complex mechanism involving ATR recruitment to RPA-coated single-stranded DNA via its binding partner ATRIP and stimulation o...
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Article
SCAI promotes DNA double-strand break repair in distinct chromosomal contexts
Hansen et al. find that SCAI (suppressor of cancer cell invasion) is a 53BP1-binding protein that acts to repair in heterochromatin and to facilitate meiotic recombination in germ cells.