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| Open AccessDNA repair glycosylase hNEIL1 triages damaged bases via competing interaction modes
hNEIL1 (human endonuclease VIII-like 1) is a broadly specific DNA glycosylase for base excision repair. Here, the authors show that hNEIL1 can assume activated or triage conformations: the structural basis for the mechanism that enables broad specificity and reduces futile repair of normal bases.
- Menghao Liu
- , Jun Zhang
- & Chengqi Yi
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Article
| Open AccessAlkyladenine DNA glycosylase associates with transcription elongation to coordinate DNA repair with gene expression
How genome stability is maintained at regions of active transcription is currently not entirely clear. Here, the authors reveal an association between base excision repair factors and transcription elongation to modulate DNA repair.
- Nicola P. Montaldo
- , Diana L. Bordin
- & Barbara van Loon
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Article
| Open AccessStructure of the error-prone DNA ligase of African swine fever virus identifies critical active site residues
The DNA ligase of African swine fever virus is one of the most error-prone ligases identified to date, but underlying molecular details are lacking. Here, Chen et al. report four AsfvLIG:DNA structures and identify a unique N-terminal domain and four unique active site residues that are crucial for its catalytic efficiency.
- Yiqing Chen
- , Hehua Liu
- & Jianhua Gan
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Article
| Open AccessPARP1 and PARP2 stabilise replication forks at base excision repair intermediates through Fbh1-dependent Rad51 regulation
PARP1 has a well characterised role in DNA break repair and base excision repair, whereas the role of PARP2 is less well understood. Here, the authors show a requirement for PARP2 in stabilising replication forks that encounter base excision repair intermediates.
- George E. Ronson
- , Ann Liza Piberger
- & Nicholas D. Lakin
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Article
| Open AccessDNA Ligase C and Prim-PolC participate in base excision repair in mycobacteria
Ligase D is a conserved DNA repair protein complex that repairs double-strand breaks in stationary phase prokaryotes. Here the authors show that orthologous Ligase C has a role in base excision repair during stationary phase.
- Przemysław Płociński
- , Nigel C. Brissett
- & Aidan J. Doherty
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Article
| Open AccessMammalian APE1 controls miRNA processing and its interactome is linked to cancer RNA metabolism
APE1 plays an important role in the cellular response to oxidative stress, and mutations are linked to tumor progression and chemoresistance. Here, the authors characterize the interactions of APE1 with RNA and demonstrate a role in microRNA processing.
- Giulia Antoniali
- , Fabrizio Serra
- & Gianluca Tell
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Article
| Open AccessA domain in human EXOG converts apoptotic endonuclease to DNA-repair exonuclease
Human EXOG is crucial for mitochondrial DNA repair. Here the authors present the crystal structures of hEXOG in apo form and as DNA complex and suggest a `tape-measure' activity to generate optimal substrates for mitochondrial base excision repair.
- Michal R. Szymanski
- , Wangsheng Yu
- & Y. Whitney Yin
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Article
| Open AccessOxidized nucleotide insertion by pol β confounds ligation during base excision repair
Oxidative stress in cells leads to the oxidations of DNA precursors. Here the authors show that these oxidized precursors can be incorporatedin vivoduring base excision repair, leading to DNA breaks and cytotoxicity.
- Melike Çağlayan
- , Julie K. Horton
- & Samuel H. Wilson
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Article
| Open AccessCrosstalk between MSH2–MSH3 and polβ promotes trinucleotide repeat expansion during base excision repair
The expansion of trinucleotide repeats can have detrimental effects and give rise to a range of human diseases. Here the authors report that the mismatch repair and the base excision repair machinery can operate together to promote expansion during lesion removal.
- Yanhao Lai
- , Helen Budworth
- & Yuan Liu
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Article
| Open AccessBiochemical reconstitution of TET1–TDG–BER-dependent active DNA demethylation reveals a highly coordinated mechanism
Cytosine methylation is a dynamic DNA modification with the involvement of the base excision repair pathway suspected to be involved in demethylation. Here the authors show that TET1 and TDG interact to target modified bases and coordinate BER to avoid double strand breaks.
- Alain R. Weber
- , Claudia Krawczyk
- & Primo Schär
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Article
| Open AccessImpact of ribonucleotide incorporation by DNA polymerases β and λ on oxidative base excision repair
Oxidative stress is a common source of DNA damage and is repaired by the base excision repair machinery, including polymerase beta. Here the authors find that polymerase beta, and to a lesser extent lambda, can mistakenly incorporate ribonucleotides during synthesis.
- Emmanuele Crespan
- , Antonia Furrer
- & Giovanni Maga
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Article
| Open AccessBase excision repair AP endonucleases and mismatch repair act together to induce checkpoint-mediated autophagy
The chemotherapeutic drug 5-fluorouracil causes cell toxicity by inducing DNA lesions. Here, SenGupta et al. use C. elegansto show that components of the base excision repair and the mismatch repair pathways function together in the response to 5-fluorouracil, resulting in activation of the DNA damage checkpoint and induction of autophagy.
- Tanima SenGupta
- , Maria Lyngaas Torgersen
- & Hilde Nilsen