Publications

@article{sultanova_optimising_2025,

title = {Optimising Age-Specific Insulin Signalling to Slow Down Reproductive Ageing Increases Fitness in Different Nutritional Environments},

author = {Zahida Sultanova and Aykut Shen and Katarzyna Hencel and Hanne Carlsson and Zoe Crighton and Daniel Clifton and Alper Akay and Alexei A. Maklakov},

url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/acel.14481},

doi = {10.1111/acel.14481},

issn = {1474-9726},

year  = {2025},

date = {2025-01-01},

urldate = {2025-01-30},

journal = {Aging Cell},

volume = {n/a},

number = {n/a},

pages = {e14481},

abstract = {The developmental theory of ageing proposes that age-specific decline in the force of natural selection results in suboptimal levels of gene expression in adulthood, leading to functional senescence. This theory explicitly predicts that optimising gene expression in adulthood can ameliorate functional senescence and improve fitness. Reduced insulin/IGF-1 signalling (rIIS) extends the reproductive lifespan of Caenorhabditis elegans at the cost of reduced reproduction. Here, we show that adulthood-only rIIS improves late-life reproduction without any detrimental effects on other life-history traits in both benign and stressful conditions. Remarkably, we show that rIIS additively extends late-life reproduction and lifespan when animals are exposed to a fluctuating food environment—intermittent fasting (IF)—resulting in reduced food intake in early adulthood. Full factorial genome-wide RNA-Seq across the life course demonstrated that IF and rIIS modulate the age-specific expression of pro-longevity genes. IF, rIIS and combined IF + rIIS treatment downregulated genes involved in biosynthesis in early life and differentially regulated immunity genes in later life. Importantly, combined IF + rIIS treatment uniquely regulated a large cluster of genes in mid-life that are associated with immune response. These results suggest that optimising gene expression in adulthood can decelerate reproductive ageing and increase fitness.},

note = {_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/acel.14481},

keywords = {ageing, developmental theory of ageing, life-history evolution, trade-offs},

pubstate = {published},

tppubtype = {article}

}

@article{shen_u6_2024,

title = {U6 snRNA m6A modification is required for accurate and efficient splicing of C. elegans and human pre-mRNAs},

author = {Aykut Shen and Katarzyna Hencel and Matthew T Parker and Robyn Scott and Roberta Skukan and Aduragbemi S Adesina and Carey L Metheringham and Eric A Miska and Yunsun Nam and Wilfried Haerty and Gordon G Simpson and Alper Akay},

url = {https://doi.org/10.1093/nar/gkae447},

doi = {10.1093/nar/gkae447},

issn = {0305-1048},

year  = {2024},

date = {2024-05-01},

urldate = {2024-05-29},

journal = {Nucleic Acids Research},

pages = {gkae447},

abstract = {pre-mRNA splicing is a critical feature of eukaryotic gene expression. Both cis- and trans-splicing rely on accurately recognising splice site sequences by spliceosomal U snRNAs and associated proteins. Spliceosomal snRNAs carry multiple RNA modifications with the potential to affect different stages of pre-mRNA splicing. Here, we show that the conserved U6 snRNA m6A methyltransferase METT-10 is required for accurate and efficient cis- and trans-splicing of C. elegans pre-mRNAs. The absence of METT-10 in C. elegans and METTL16 in humans primarily leads to alternative splicing at 5′ splice sites with an adenosine at +4 position. In addition, METT-10 is required for splicing of weak 3′ cis- and trans-splice sites. We identified a significant overlap between METT-10 and the conserved splicing factor SNRNP27K in regulating 5′ splice sites with +4A. Finally, we show that editing endogenous 5′ splice site +4A positions to +4U restores splicing to wild-type positions in a mett-10 mutant background, supporting a direct role for U6 snRNA m6A modification in 5′ splice site recognition. We conclude that the U6 snRNA m6A modification is important for accurate and efficient pre-mRNA splicing.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{navarro_translational_2021,

title = {Translational adaptation to heat stress is mediated by RNA 5-methylcytosine in Caenorhabditis elegans},

author = {Isabela Cunha Navarro and Francesca Tuorto and David Jordan and Carine Legrand and Jonathan Price and Fabian Braukmann and Alan G Hendrick and Alper Akay and Annika Kotter and Mark Helm and Frank Lyko and Eric A Miska},

url = {http://dx.doi.org/10.15252/embj.2020105496},

doi = {10.15252/embj.2020105496},

issn = {0261-4189},

year  = {2021},

date = {2021-03-01},

journal = {EMBO J.},

volume = {40},

number = {6},

pages = {e105496},

abstract = {Methylation of carbon-5 of cytosines (m5 C) is a post-transcriptional 

nucleotide modification of RNA found in all kingdoms of life. While 

individual m5 C-methyltransferases have been studied, the impact of the 

global cytosine-5 methylome on development, homeostasis and stress remains 

unknown. Here, using Caenorhabditis elegans, we generated the first 

organism devoid of m5 C in RNA, demonstrating that this modification is 

non-essential. Using this genetic tool, we determine the localisation and 

enzymatic specificity of m5 C sites in the RNome in vivo. We find that 

NSUN-4 acts as a dual rRNA and tRNA methyltransferase in C. elegans 

mitochondria. In agreement with leucine and proline being the most 

frequently methylated tRNA isoacceptors, loss of m5 C impacts the decoding 

of some triplets of these two amino acids, leading to reduced translation 

efficiency. Upon heat stress, m5 C loss leads to ribosome stalling at UUG 

triplets, the only codon translated by an m5 C34-modified tRNA. This leads 

to reduced translation efficiency of UUG-rich transcripts and impaired 

fertility, suggesting a role of m5 C tRNA wobble methylation in the 

adaptation to higher temperatures.},

note = {Publisher: John Wiley & Sons, Ltd},

keywords = {5-methylcytosine, Caenorhabditis elegans, NSUN, RNA modifications, translation efficiency},

pubstate = {published},

tppubtype = {article}

}

@article{berkyurek_rna_2021,

title = {The RNA polymerase II subunit RPB-9 recruits the integrator complex to terminate Caenorhabditis elegans piRNA transcription},

author = {Ahmet C Berkyurek and Giulia Furlan and Lisa Lampersberger and Toni Beltran and Eva-Maria Weick and Emily Nischwitz and Isabela Cunha Navarro and Fabian Braukmann and Alper Akay and Jonathan Price and Falk Butter and Peter Sarkies and Eric A Miska},

url = {http://dx.doi.org/10.15252/embj.2020105565},

doi = {10.15252/embj.2020105565},

issn = {0261-4189},

year  = {2021},

date = {2021-03-01},

journal = {EMBO J.},

volume = {40},

number = {5},

pages = {e105565},

abstract = {PIWI-interacting RNAs (piRNAs) are genome-encoded small RNAs that regulate 

germ cell development and maintain germline integrity in many animals. 

Mature piRNAs engage Piwi Argonaute proteins to silence complementary 

transcripts, including transposable elements and endogenous genes. piRNA 

biogenesis mechanisms are diverse and remain poorly understood. Here, we 

identify the RNA polymerase II (RNA Pol II) core subunit RPB-9 as required 

for piRNA-mediated silencing in the nematode Caenorhabditis elegans. We 

show that rpb-9 initiates heritable piRNA-mediated gene silencing at two 

DNA transposon families and at a subset of somatic genes in the germline. 

We provide genetic and biochemical evidence that RPB-9 is required for 

piRNA biogenesis by recruiting the Integrator complex at piRNA genes, 

hence promoting transcriptional termination. We conclude that, as a part 

of its rapid evolution, the piRNA pathway has co-opted an ancient 

machinery for high-fidelity transcription.},

note = {Publisher: EMBO},

keywords = {integrator, piRNAs, RNA polymerase II, rpb-9, transcription termination},

pubstate = {published},

tppubtype = {article}

}

@article{kranse_toward_2021,

title = {Toward genetic modification of plant-parasitic nematodes: delivery of macromolecules to adults and expression of exogenous mRNA in second stage juveniles},

author = {Olaf Kranse and Helen Beasley and Sally Adams and Andre Pires-daSilva and Christopher Bell and Catherine J Lilley and Peter E Urwin and David Bird and Eric Miska and Geert Smant and Godelieve Gheysen and John Jones and Mark Viney and Pierre Abad and Thomas R Maier and Thomas J Baum and Shahid Siddique and Valerie Williamson and Alper Akay and Sebastian Eves-van den Akker},

url = {http://dx.doi.org/10.1093/g3journal/jkaa058},

doi = {10.1093/g3journal/jkaa058},

issn = {2160-1836},

year  = {2021},

date = {2021-02-01},

journal = {G3},

volume = {11},

number = {2},

abstract = {Plant-parasitic nematodes are a continuing threat to food security, 

causing an estimated 100 billion USD in crop losses each year. The most 

problematic are the obligate sedentary endoparasites (primarily root knot 

nematodes and cyst nematodes). Progress in understanding their biology is 

held back by a lack of tools for functional genetics: forward genetics is 

largely restricted to studies of natural variation in populations and 

reverse genetics is entirely reliant on RNA interference. There is an 

expectation that the development of functional genetic tools would 

accelerate the progress of research on plant-parasitic nematodes, and 

hence the development of novel control solutions. Here, we develop some of 

the foundational biology required to deliver a functional genetic tool kit 

in plant-parasitic nematodes. We characterize the gonads of male 

Heterodera schachtii and Meloidogyne hapla in the context of 

spermatogenesis. We test and optimize various methods for the delivery, 

expression, and/or detection of exogenous nucleic acids in plant-parasitic 

nematodes. We demonstrate that delivery of macromolecules to cyst and root 

knot nematode male germlines is difficult, but possible. Similarly, we 

demonstrate the delivery of oligonucleotides to root knot nematode 

gametes. Finally, we develop a transient expression system in 

plant-parasitic nematodes by demonstrating the delivery and expression of 

exogenous mRNA encoding various reporter genes throughout the body of H. 

schachtii juveniles using lipofectamine-based transfection. We anticipate 

these developments to be independently useful, will expedite the 

development of genetic modification tools for plant-parasitic nematodes, 

and ultimately catalyze research on a group of nematodes that threaten 

global food security.},

keywords = {genetic modification, germline, lipofection, plant-parasitic nematodes, transformation, transient expression},

pubstate = {published},

tppubtype = {article}

}

@article{suen_deps-1_2020,

title = {DEPS-1 is required for piRNA-dependent silencing and PIWI condensate organisation in Caenorhabditis elegans},

author = {Kin Man Suen and Fabian Braukmann and Richard Butler and Dalila Bensaddek and Alper Akay and Chi-Chuan Lin and Dovilė Milonaitytė and Neel Doshi and Alexandra Sapetschnig and Angus Lamond and John Edward Ladbury and Eric Alexander Miska},

url = {http://dx.doi.org/10.1038/s41467-020-18089-1},

doi = {10.1038/s41467-020-18089-1},

issn = {2041-1723},

year  = {2020},

date = {2020-08-01},

journal = {Nat. Commun.},

volume = {11},

number = {1},

pages = {4242},

abstract = {Membraneless organelles are sites for RNA biology including small 

non-coding RNA (ncRNA) mediated gene silencing. How small ncRNAs utilise 

phase separated environments for their function is unclear. We 

investigated how the PIWI-interacting RNA (piRNA) pathway engages with the 

membraneless organelle P granule in Caenorhabditis elegans. Proteomic 

analysis of the PIWI protein PRG-1 reveals an interaction with the 

constitutive P granule protein DEPS-1. DEPS-1 is not required for piRNA 

biogenesis but piRNA-dependent silencing: deps-1 mutants fail to produce 

the secondary endo-siRNAs required for the silencing of piRNA targets. We 

identify a motif on DEPS-1 which mediates a direct interaction with PRG-1. 

DEPS-1 and PRG-1 form intertwining clusters to build elongated condensates 

in vivo which are dependent on the Piwi-interacting motif of DEPS-1. 

Additionally, we identify EDG-1 as an interactor of DEPS-1 and PRG-1. Our 

study reveals how specific protein-protein interactions drive the spatial 

organisation and piRNA-dependent silencing within membraneless organelles.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{akay_identification_2019,

title = {Identification of functional long non-coding RNAs in C. elegans},

author = {Alper Akay and David Jordan and Isabela Cunha Navarro and Tomasz Wrzesinski and Chris P Ponting and Eric A Miska and Wilfried Haerty},

url = {http://dx.doi.org/10.1186/s12915-019-0635-7},

doi = {10.1186/s12915-019-0635-7},

issn = {1741-7007},

year  = {2019},

date = {2019-02-01},

journal = {BMC Biol.},

volume = {17},

number = {1},

pages = {14},

abstract = {BACKGROUND: Functional characterisation of the compact genome of the model 

organism Caenorhabditis elegans remains incomplete despite its sequencing 

20 years ago. The last decade of research has seen a tremendous increase 

in the number of non-coding RNAs identified in various organisms. While we 

have mechanistic understandings of small non-coding RNA pathways, long 

non-coding RNAs represent a diverse class of active transcripts whose 

function remains less well characterised. RESULTS: By analysing hundreds 

of published transcriptome datasets, we annotated 3392 potential lncRNAs 

including 143 multi-exonic loci that showed increased nucleotide 

conservation and GC content relative to other non-coding regions. Using 

CRISPR/Cas9 genome editing, we generated deletion mutants for ten long 

non-coding RNA loci. Using automated microscopy for in-depth phenotyping, 

we show that six of the long non-coding RNA loci are required for normal 

development and fertility. Using RNA interference-mediated gene 

knock-down, we provide evidence that for two of the long non-coding RNA 

loci, the observed phenotypes are dependent on the corresponding RNA 

transcripts. CONCLUSIONS: Our results highlight that a large section of 

the non-coding regions of the C. elegans genome remains unexplored. Based 

on our in vivo analysis of a selection of high-confidence lncRNA loci, we 

expect that a significant proportion of these high-confidence regions is 

likely to have a biological function at either the genomic or the 

transcript level.},

keywords = {Akay_Lab/lncRNA, C. elegans, CRISPR, lincRNA, lncRNA, Long non-coding RNA, Non-coding},

pubstate = {published},

tppubtype = {article}

}

@article{sarabipour_preprints_2018,

title = {Preprints are good for science and good for the public},

author = {Sarvenaz Sarabipour},

url = {http://www.nature.com/articles/d41586-018-06054-4},

doi = {10.1038/d41586-018-06054-4},

issn = {0028-0836},

year  = {2018},

date = {2018-08-01},

urldate = {2018-08-29},

journal = {Nature},

volume = {560},

number = {7720},

pages = {553},

abstract = {Discover the world’s best science and medicine textbar Nature.com},

note = {Publisher: Nature Publishing Group},

keywords = {Communication, Media, Publishing},

pubstate = {published},

tppubtype = {article}

}

@article{akay_helicase_2017,

title = {The Helicase Aquarius/EMB-4 Is Required to Overcome Intronic Barriers to Allow Nuclear RNAi Pathways to Heritably Silence Transcription},

author = {Alper Akay and Tomas Di Domenico and Kin M Suen and Amena Nabih and Guillermo E Parada and Mark Larance and Ragini Medhi and Ahmet C Berkyurek and Xinlian Zhang and Christopher J Wedeles and Konrad L M Rudolph and Jan Engelhardt and Martin Hemberg and Ping Ma and Angus I Lamond and Julie M Claycomb and Eric A Miska},

url = {http://dx.doi.org/10.1016/j.devcel.2017.07.002},

doi = {10.1016/j.devcel.2017.07.002},

issn = {1534-5807},

year  = {2017},

date = {2017-08-01},

journal = {Dev. Cell},

volume = {42},

number = {3},

pages = {241–255.e6},

abstract = {Small RNAs play a crucial role in genome defense against transposable 

elements and guide Argonaute proteins to nascent RNA transcripts to induce 

co-transcriptional gene silencing. However, the molecular basis of this 

process remains unknown. Here, we identify the conserved RNA helicase 

Aquarius/EMB-4 as a direct and essential link between small RNA pathways 

and the transcriptional machinery in Caenorhabditis elegans. Aquarius 

physically interacts with the germline Argonaute HRDE-1. Aquarius is 

required to initiate small-RNA-induced heritable gene silencing. HRDE-1 

and Aquarius silence overlapping sets of genes and transposable elements. 

Surprisingly, removal of introns from a target gene abolishes the 

requirement for Aquarius, but not HRDE-1, for small RNA-dependent gene 

silencing. We conclude that Aquarius allows small RNA pathways to compete 

for access to nascent transcripts undergoing co-transcriptional splicing 

in order to detect and silence transposable elements. Thus, Aquarius and 

HRDE-1 act as gatekeepers coordinating gene expression and genome defense.},

keywords = {C. elegans, epigenetic inheritance, nuclear RNAi, piRNA, Piwi, RNA processing, RNAi, splicing, transcription, transposable elements},

pubstate = {published},

tppubtype = {article}

}

@article{van_delft_profile_2017,

title = {The Profile and Dynamics of RNA Modifications in Animals},

author = {Pieter Delft and Alper Akay and Sabrina M Huber and Christoph Bueschl and Konrad L M Rudolph and Tomás Di Domenico and Rainer Schuhmacher and Eric A Miska and Shankar Balasubramanian},

url = {http://dx.doi.org/10.1002/cbic.201700093},

doi = {10.1002/cbic.201700093},

issn = {1439-4227},

year  = {2017},

date = {2017-06-01},

journal = {Chembiochem},

volume = {18},

number = {11},

pages = {979–984},

abstract = {More than a hundred distinct modified nucleosides have been identified in 

RNA, but little is known about their distribution across different 

organisms, their dynamic nature and their response to cellular and 

environmental stress. Mass-spectrometry-based methods have been at the 

forefront of identifying and quantifying modified nucleosides. However, 

they often require synthetic reference standards, which do not exist in 

the case of many modified nucleosides, and this therefore impedes their 

analysis. Here we use a metabolic labelling approach to achieve rapid 

generation of bio-isotopologues of the complete Caenorhabditis elegans 

transcriptome and its modifications and use them as reference standards to 

characterise the RNA modification profile in this multicellular organism 

through an untargeted liquid-chromatography tandem high-resolution mass 

spectrometry (LC-HRMS) approach. We furthermore show that several of these 

RNA modifications have a dynamic response to environmental stress and 

that, in particular, changes in the tRNA wobble base modification 

5-methoxycarbonylmethyl-2-thiouridine (mcm5 s2 U) lead to codon-biased 

gene-expression changes in starved animals.},

keywords = {Caenorhabditis elegans, isotopic labeling, mass spectrometry, RNA modifications, stress response, tRNA},

pubstate = {published},

tppubtype = {article}

}

@article{akay_e_2015,

title = {E. coli OxyS non-coding RNA does not trigger RNAi in C. elegans},

author = {Alper Akay and Peter Sarkies and Eric A Miska},

url = {http://dx.doi.org/10.1038/srep09597},

doi = {10.1038/srep09597},

issn = {2045-2322},

year  = {2015},

date = {2015-04-01},

journal = {Sci. Rep.},

volume = {5},

pages = {9597},

abstract = {The discovery of RNA interference (RNAi) in C. elegans has had a major 

impact on scientific research, led to the rapid development of RNAi tools 

and has inspired RNA-based therapeutics. Astonishingly, nematodes, 

planaria and many insects take up double-stranded RNA (dsRNA) from their 

environment to elicit RNAi; the biological function of this mechanism is 

unclear. Recently, the E. coli OxyS non-coding RNA was shown to regulate 

gene expression in C. elegans when E. coli is offered as food. This was 

surprising given that C. elegans is unlikely to encounter E. coli in 

nature. To directly test the hypothesis that the E. coli OxyS non-coding 

RNA triggers the C. elegans RNAi pathway, we sequenced small RNAs from C. 

elegans after feeding with bacteria. We clearly demonstrate that the OxyS 

non-coding RNA does not trigger an RNAi response in C. elegans. We 

conclude that the biology of environmental RNAi remains to be discovered.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{akay_rna-binding_2013,

title = {RNA-binding protein GLD-1/quaking genetically interacts with the mir-35 and the let-7 miRNA pathways in Caenorhabditis elegans},

author = {Alper Akay and Ashley Craig and Nicolas Lehrbach and Mark Larance and Ehsan Pourkarimi and Jane E Wright and Angus Lamond and Eric Miska and Anton Gartner},

url = {http://dx.doi.org/10.1098/rsob.130151},

doi = {10.1098/rsob.130151},

issn = {2046-2441},

year  = {2013},

date = {2013-11-01},

journal = {Open Biol.},

volume = {3},

number = {11},

pages = {130151},

abstract = {Messenger RNA translation is regulated by RNA-binding proteins and small 

non-coding RNAs called microRNAs. Even though we know the majority of 

RNA-binding proteins and microRNAs that regulate messenger RNA expression, 

evidence of interactions between the two remain elusive. The role of the 

RNA-binding protein GLD-1 as a translational repressor is well studied 

during Caenorhabditis elegans germline development and maintenance. 

Possible functions of GLD-1 during somatic development and the mechanism 

of how GLD-1 acts as a translational repressor are not known. Its human 

homologue, quaking (QKI), is essential for embryonic development. Here, we 

report that the RNA-binding protein GLD-1 in C. elegans affects multiple 

microRNA pathways and interacts with proteins required for microRNA 

function. Using genome-wide RNAi screening, we found that nhl-2 and vig-1, 

two known modulators of miRNA function, genetically interact with GLD-1. 

gld-1 mutations enhance multiple phenotypes conferred by mir-35 and let-7 

family mutants during somatic development. We used stable isotope 

labelling with amino acids in cell culture to globally analyse the changes 

in the proteome conferred by let-7 and gld-1 during animal development. We 

identified the histone mRNA-binding protein CDL-1 to be, in part, 

responsible for the phenotypes observed in let-7 and gld-1 mutants. The 

link between GLD-1 and miRNA-mediated gene regulation is further supported 

by its biochemical interaction with ALG-1, CGH-1 and PAB-1, proteins 

implicated in miRNA regulation. Overall, we have uncovered genetic and 

biochemical interactions between GLD-1 and miRNA pathways.},

keywords = {Caenorhabditis elegans, gld-1, let-7, miRNA, SILAC},

pubstate = {published},

tppubtype = {article}

}

@article{gartner_stress_2013,

title = {Stress response: anything that doesn't kill you makes you stronger},

author = {A Gartner and A Akay},

url = {https://www.sciencedirect.com/science/article/pii/S0960982213011834},

issn = {0960-9822},

year  = {2013},

date = {2013-01-01},

journal = {Curr. Biol.},

abstract = {Hormesis occurs when a low-level stress elicits responses that protect 

against subsequent exposure to severe stress. Such protection often 

affects a variety of stress conditions. For instance, oxidative and 

thermal stress can extend lifespan by hormetic mechanisms [1]. By analogy, 

surviving continuous …},

note = {Publisher: Elsevier},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{feitsma_alkylation_2008,

title = {Alkylation damage causes MMR-dependent chromosomal instability in vertebrate embryos},

author = {Harma Feitsma and Alper Akay and Edwin Cuppen},

url = {http://dx.doi.org/10.1093/nar/gkn341},

doi = {10.1093/nar/gkn341},

issn = {0305-1048},

year  = {2008},

date = {2008-07-01},

journal = {Nucleic Acids Res.},

volume = {36},

number = {12},

pages = {4047–4056},

abstract = {S(N)1-type alkylating agents, like N-methyl-N-nitrosourea (MNU) and 

N-ethyl-N-nitrosourea (ENU), are potent mutagens. Exposure to alkylating 

agents gives rise to O(6)-alkylguanine, a modified base that is recognized 

by DNA mismatch repair (MMR) proteins but is not repairable, resulting in 

replication fork stalling and cell death. We used a somatic mutation 

detection assay to study the in vivo effects of alkylation damage on 

lethality and mutation frequency in developing zebrafish embryos. 

Consistent with the damage-sensing role of the MMR system, mutant embryos 

lacking the MMR enzyme MSH6 displayed lower lethality than wild-type 

embryos after exposure to ENU and MNU. In line with this, 

alkylation-induced somatic mutation frequencies were found to be higher in 

wild-type embryos than in the msh6 loss-of-function mutants. These 

mutations were found to be chromosomal aberrations that may be caused by 

chromosomal breaks that arise from stalled replication forks. As these 

chromosomal breaks arise at replication, they are not expected to be 

repaired by non-homologous end joining. Indeed, Ku70 loss-of-function 

mutants were found to be equally sensitive to ENU as wild-type embryos. 

Taken together, our results suggest that in vivo alkylation damage results 

in chromosomal instability and cell death due to aberrantly processed 

MMR-induced stalled replication forks.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}