EGAGenomicsIllumina HiSeq 2000;https://ega-archive.org/datasets/EGAD000010016332EGA dataset EGAD00001001633EGADNA lesions encountered by replicative polymerases threaten genome stability and cell cycle progression. Here we report the identification of mutations in TRAIP, encoding an E3 RING ubiquitin ligase, in patients with microcephalic primordial dwarfism. We establish that TRAIP relocalizes to sites of DNA damage, where it is required for optimal phosphorylation of H2AX and RPA2 during S-phase in response to ultraviolet (UV) irradiation, as well as fork progression through UV-induced DNA lesions. TRAIP is necessary for efficient cell cycle progression and mutations in TRAIP therefore limit cellular proliferation, providing a potential mechanism for microcephaly and dwarfism phenotypes. Human genetics thus identifies TRAIP as a component of the DNA damage response to replication-blocking DNA lesions.TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism.Harley Margaret E ME, Murina Olga O, Leitch Andrea A, Higgs Martin R MR, Bicknell Louise S LS, Yigit Gökhan G, Blackford Andrew N AN, Zlatanou Anastasia A, Mackenzie Karen J KJ, Reddy Kaalak K, Halachev Mihail M, McGlasson Sarah S, Reijns Martin A M MAM, Fluteau Adeline A, Martin Carol-Anne CA, Sabbioneda Simone S, Elcioglu Nursel H NH, Altmüller Janine J, Thiele Holger H, Greenhalgh Lynn L, Chessa Luciana L, Maghnie Mohamad M, Salim Mahmoud M, Bober Michael B MB, Nürnberg Peter P, Jackson Stephen P SP, Hurles Matthew E ME, Wollnik Bernd B, Stewart Grant S GS, Jackson Andrew P APVasp, VASP, Data Set., DmelCG15112, ENHANCER OF ATNSI ACTIVITY, MENA, NDPP1, l(2)02029, Enb, enb, ENA, Ena, CG15112, ENA/VASPTRIP, WES, BamF, bim, biml, BamC, HCAP, bim-beta6, bam, ham, BOD, alpha, CDLS3, BMH, fs(3)neo61, Trip, CG10422, BIM, Client., Patient, Bam-C, Clients, BAM, Bam, SMC3L1, bim-beta7, bod, DmelCG10422, RNF206, CSPG6, bimelTRIP, isolated growth hormone deficiency type 1A., isolated, Genomes, ILLIG type growth hormone deficiency, congenital IGHD, Illig-type Growth hormone deficiency, non-acquired isolated growth hormone deficiency, pituitary dwarfism 1, IGHD 1A, congenital isolated GH deficiency, IGHD1A, whole genome, Growth hormone deficiency, response to DNA damage stimulus, type IA, isolated Growth hormone deficiency, congenital isolated growth hormone deficiency, Trip, isolated growth hormone deficiency, DNA Damage Response, type 1A, RNF206, isolated autosomal recessive, autosomal recessiveTRIP, AI325195, Progress Reports, phosphorylation, DmelCG4087, Mutations, BUF1, Microlissencephalies, Summary Report, replicon protein A2, RLA1_DROME, ATRPA2, CG5499, Summary Reports, H2A|X, HIS2AV, Cell Division Cycles, thymus nucleic acid, High Mobility Protein 20, Short stature, Genomes, Progress Report, S-phase, CG9273, Dwarfism, Ubiquitin-related 1, h2AvD, HIS2AVD, Ligase, Progress, Trip, APF-1, l(3)05146, Field Reports, Proportionate dwarfism, Cell Cycles, Rpo1-2, Double-Stranded DNA, deoxyribonucleic acids, DNAn, severe, H2AX, DmelCG5499, H2ax, H2AZ, CG4087, microencephaly, h2a/x, dRPA2, rpP2, H2A, Double-Stranded, Rf-A2, response to DNA damage stimulus, rpa2, CEP52, Microlissencephaly, rp21C, Division Cycles, H2Av, SPCC584.06c, extreme, RP-A p32, (Deoxyribonucleotide)n+m, RP-A p34, SRP3, Investigative Report, h2ax, Hist5-2ax, Rplp1, desoxyribose nucleic acid, Ubiq, H2AV, H2av, Ubiquitin, l(3)810, DNA Injury, DNA Injuries, 128kDa, RpA2, AA409079, Division Cycle, H2A.Z, Deoxyribonucleic acids., H2A.X, Field, H2a.V, Human Ubiquitin, whole genome, DmelCG9273, Phenotypes, Report, RpP2, Genotoxic, Patient, RPA2, T28I24.22, Proliferation, ds DNA, H2A/X, h2a.x, DNA, T28I24_22, rpA2, 153194_at, RPA116, Proliferating, DNS, (Deoxyribonucleotide)n, SUPPRESSOR OF ROS1, Microcephaly, Nanism, Hist2av, Synthetases, ATP Dependent Proteolysis Factor 1, gamma-His2Av, Ubiquitin carboxyl extension protein 80, Deoxyribonucleic acids, Human, His2, microcephaly (disease), Investigative, Deoxyribonucleic Acid, LP1, Cycle, DNA Damage Response, HMG-20, ATRPA32A, ROR1, Cycles, Injury, H2A.F/Z, H2AV_DROM, gamma-HIS2AV, proliferating, Severe short stature, Cell Division Cycle, cell-division cycle, HisH2Av, Double Stranded, Deoxyribonucleic acid, Cell Division, Hist, M(2)21C1-2, 40S ribosomal protein S27a, H2AvD, Clients, RPA32A, ubiquitin, HIS, His, (Deoxyribonucleotide)m, Investigative Reports, AW228881, protein tagging activity, Severe Congenital, D630020H17Rik, Severe Congenital Microcephalies, l(3)97Dd, H2avD, DNAn+1, Phosphorylations, gammaH2ax, his, Genetics, Client, Cell, Ubiquitin A-52 residue ribosomal protein fusion product 1, gamma-H2Av, Severe Congenital Microcephaly, Ubiquitin-related 2, Research Reports, Synthetase, ds-DNA, RNF206, ATP-Dependent Proteolysis Factor 1, gammaH2Av, small calvarium, covalent modifier, Genotoxic Stress, RRN2, RPA135, Congenital Microcephaly, l(3)L1602, RPA32, RPA34, microcephalus, Microcephalies, DNA Lesion, His2AvD, microcephaly, DNA Lesions, AU020965, 5499, M(2)21C, Reports, 60S ribosomal protein L40, ligase, REPA2, Congenital Microcephalies, His2AV, Stress, Desoxyribonukleinsaeure, Ubiquitin-related, Summary, Severe, Field Reportfalseena-DATASET-MRCHGUIGMM-07-10-2015-09:16:27:050-356 - samplesBAM files for two WES TRAIP patients2017-07-26 15:39:26EGAD00001001633960626595769EGAC00001000393EGAS00001001501