Featured
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Article |
Structural basis of long-range to short-range synaptic transition in NHEJ
Double-strand DNA break repair by the non-homologous end joining pathway involves the transition from a complex that bridges the DNA ends to a complex that aligns the DNA for ligation through the dissociation of the kinase subunits of the DNA-PK complexes.
- Siyu Chen
- , Linda Lee
- & Yuan He
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Article |
DNA-PKcs has KU-dependent function in rRNA processing and haematopoiesis
The catalytic subunit of DNA-PK autophosphorylates and contributes to ribosome biogenesis and haematopoiesis by binding to the U3 small nucleolar RNA.
- Zhengping Shao
- , Ryan A. Flynn
- & Eliezer Calo
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Letter |
53BP1 cooperation with the REV7–shieldin complex underpins DNA structure-specific NHEJ
The specificity of 53BP1 and its co-factors for particular DNA substrates during non-homologous end joining (NHEJ) derives from REV7–shieldin, a four-subunit DNA-binding complex that is required for REV7-dependent NHEJ but not for REV7-dependent DNA interstrand cross-link repair.
- Hind Ghezraoui
- , Catarina Oliveira
- & J. Ross Chapman
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Letter |
Regulation of DNA repair pathway choice in S and G2 phases by the NHEJ inhibitor CYREN
CYREN is a direct inhibitor of classical non-homologous end joining that promotes error-free repair by homologous recombination during the S and G2 phases of the cell cycle.
- Nausica Arnoult
- , Adriana Correia
- & Jan Karlseder
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Letter |
Mammalian polymerase θ promotes alternative NHEJ and suppresses recombination
Next-generation sequencing technology is used to show that the error-prone polymerase θ (Polθ) is needed to promote alternative non-homologous end joining at telomeres, and during chromosomal translocations, while counteracting homologous recombination; inhibition of Polθ represents a potential therapeutic strategy for tumours that have mutations in homology-directed repair genes.
- Pedro A. Mateos-Gomez
- , Fade Gong
- & Agnel Sfeir
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Letter |
Homologous-recombination-deficient tumours are dependent on Polθ-mediated repair
In studies in mammalian cells, polymerase theta (Polθ, also known as POLQ) is identified as the polymerase responsible for non-homologous end joining DNA repair; this DNA repair pathway acts in many tumours when homologous recombination is inactivated and the identification of the polymerase responsible may aid the development of new therapeutic approaches.
- Raphael Ceccaldi
- , Jessica C. Liu
- & Alan D. D’Andrea
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Letter |
Bidirectional resection of DNA double-strand breaks by Mre11 and Exo1
- Valerie Garcia
- , Sarah E. L. Phelps
- & Matthew J. Neale
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Letter |
ATM damage response and XLF repair factor are functionally redundant in joining DNA breaks
Although loss of XLF, a classical non-homologous DNA end-joining (NHEJ) repair factor, shows strong effects in non-lymphoid cells, in lymphoid cells its absence has only modest effects on V(D)J recombination. This study now shows that in lymphoid cells, two other repair factors — ATM kinase and histone protein H2AX — have functional redundancy with XLF. Thus, mice deficient in both ATM and XLF have compromised conventional NHEJ, although alternative end-joining is retained. The results hint that the redundant function in end-joining that XLF has with both ATM and H2AX may have to do with an ATM role in chromatin accessibility.
- Shan Zha
- , Chunguang Guo
- & Frederick W. Alt
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Letter |
Ku is a 5′-dRP/AP lyase that excises nucleotide damage near broken ends
Most agents that generate breaks in DNA leave 'dirty ends' that cannot be joined immediately; instead, intervening steps are required to restore the integrity of nucleotides at the break. Here it is shown that the non-homologous end joining pathway requires a 5′-dRP/AP lyase activity to remove abasic sites at double-strand breaks. Surprisingly, this activity is catalysed by the Ku70 protein, which, together with its partner Ku86, had been thought only to recognize broken DNA ends and to recruit other factors that process ends.
- Steven A. Roberts
- , Natasha Strande
- & Dale A. Ramsden