Abstract：
:The human Y-family DNA polymerases, Poliota, Poleta, and Polkappa, function in promoting replication through DNA lesions. However, because of their low fidelity, any involvement of these polymerases in DNA synthesis during base excision repair (BER) would be highly mutagenic. Mechanisms, therefore, must exist to exclude their participation in BER. Here, we show that although Poliota, Poleta, and Polkappa are all able to form a covalent Schiff base intermediate with the 5'-deoxyribose phosphate (5'-dRP) residue that results from the incision of DNA at an abasic site by an AP endonuclease, they all lack the ability for the subsequent catalytic removal of the 5'-dRP group. Instead, the covalent trapping of these polymerases by the 5'-dRP residue inhibits their DNA synthetic activity during BER. The unprecedented ability of these polymerases for robust Schiff base formation without the release of the 5'-dRP product provides a means of preventing their participation in the DNA synthetic step of BER, thereby avoiding the high incidence of mutagenesis and carcinogenesis that would otherwise occur.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Haracska L,Prakash L,Prakash Sdoi
10.1101/gad.1146103subject
Has Abstractpub_date
2003-11-15 00:00:00pages
2777-85issue
22eissn
0890-9369issn
1549-5477pii
17/22/2777journal_volume
17pub_type
杂志文章abstract：:To find new genes that influence liver lipid mass, we performed a genetic screen for zebrafish mutants with hepatic steatosis, a pathological accumulation of fat. The red moon (rmn) mutant develops hepatic steatosis as maternally deposited yolk is depleted. Conversely, hepatic steatosis is suppressed in rmn mutants by...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.180968.111
更新日期：2012-02-01 00:00:00
abstract：:Fibro-adipogenic progenitors (FAPs) reside in the muscle, where they facilitate myofiber regeneration. Under normal conditions, FAPs lack myogenic potential and thus do not directly contribute to regenerated myofibers. Surprisingly, Saccone and colleagues (pp. 841-857) demonstrated that the dystrophic muscle environme...
journal_title：Genes & development
pub_type： 评论,杂志文章
doi：10.1101/gad.241182.114
更新日期：2014-04-15 00:00:00
abstract：:Although the human U2 and U6 snRNA genes are transcribed by different RNA polymerases (i.e., RNA polymerases II and III, respectively), their promoters are very similar in structure. Both contain a proximal sequence element (PSE) and an octamer motif-containing enhancer, and these elements are interchangeable between ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.5.8.1477
更新日期：1991-08-01 00:00:00
abstract：:The NF-kappa B transcription factor complex is comprised of two subunits, p50 and p65, that share significant homology to the rel oncogene. We have isolated a cDNA encoding a novel 66-kD rel-related protein, designated I-Rel. Unlike other rel-related proteins, I-Rel does not interact with DNA. I-Rel forms heterodimers...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.6.5.745
更新日期：1992-05-01 00:00:00
abstract：:An RNA-based gene silencing pathway that protects bacteria and archaea from viruses and other genome invaders is hypothesized to arise from guide RNAs encoded by CRISPR loci and proteins encoded by the cas genes. CRISPR loci contain multiple short invader-derived sequences separated by short repeats. The presence of v...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1742908
更新日期：2008-12-15 00:00:00
abstract：:Although the transporter-like protein Patched (Ptc) is genetically implicated in reception of the extracellular Hedgehog (Hh) protein signal, a clear definition of the Hh receptor is complicated by the existence of additional Hh-binding proteins and, in Drosophila, by the lack of physical evidence for direct binding o...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1870310
更新日期：2010-01-01 00:00:00
abstract：:Ribonucleotide reductase activity is essential for progression through the cell cycle, catalyzing the rate-limiting step for the production of deoxyribonucleotides needed for DNA synthesis. The enzymatic activity of the enzyme fluctuates in the cell cycle with an activity maximum in S phase. We have identified and cha...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.4.5.740
更新日期：1990-05-01 00:00:00
abstract：:Activated Ras initiates a cascade of sequential phosphorylation events, including the protein kinases Raf, MEK, and MAP kinase. The Let-60 Ras-mediated signal transduction pathway controls vulval induction in Caenorhabditis elegans. Both Lin-45 Raf and Sur-1 MAP kinase have been determined to be essential factors duri...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.9.6.742
更新日期：1995-03-15 00:00:00
abstract：:Alu repetitive sequences are the most abundant short interspersed DNA elements in the human genome. Full-length Alu elements are composed of two tandem sequence monomers, the left and right Alu arms, both derived from the 7SL signal recognition particle RNA. Since Alu elements are common in protein-coding genes, they ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.197467.112
更新日期：2012-09-01 00:00:00
abstract：:The v-erbA oncogene of avian erythroblastosis virus (AEV) encodes a ligand-independent mutated version of the chicken c-erbA alpha-encoded thyroid hormone receptor. The v-erbA gene product, a 75-kD gag/v-erbA fusion protein, is phosphorylated on Ser-16/17 of its v-erbA-encoded domain, and phosphorylation at this site ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.4.10.1663
更新日期：1990-10-01 00:00:00
abstract：:Alternative polyadenylation (APA) is widespread in neuronal development and activity-mediated neural plasticity. However, the underlying molecular mechanisms are largely unknown. We used systematic genetic studies and genome-wide surveys of the transcriptional landscape to identify a context-dependent regulatory pathw...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.266650.115
更新日期：2015-11-15 00:00:00
abstract：:The mitotic kinase Aurora A (Aur-A) is required for formation of a bipolar mitotic spindle and accurate chromosome segregation. In somatic cells, Aur-A protein and kinase activity levels peak during mitosis, and Aur-A is degraded during mitotic exit. Here, we investigated how Aur-A protein and kinase activity levels a...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1007302
更新日期：2002-09-01 00:00:00
abstract：:The epidemic of obesity and diabetes is causing an increased incidence of dyslipidemia-related heart failure. While the primary etiology of lipotoxic cardiomyopathy is an elevation of lipid levels resulting from an imbalance in energy availability and expenditure, increasing evidence suggests a relationship between dy...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1992411
更新日期：2011-01-15 00:00:00
abstract：:Gut homeostasis is controlled by both immune and developmental mechanisms, and its disruption can lead to inflammatory disorders or cancerous lesions of the intestine. While the impact of bacteria on the mucosal immune system is beginning to be precisely understood, little is known about the effects of bacteria on gut...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1827009
更新日期：2009-10-01 00:00:00
abstract：:Pax6 is a key transcription factor in eye development, particularly in lens development, but its molecular action has not been clarified. We demonstrate that Pax6 initiates lens development by forming a molecular complex with SOX2 on the lens-specific enhancer elements, e.g., the delta-crystallin minimal enhancer DC5....
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.887101
更新日期：2001-05-15 00:00:00
abstract：:Human ELAV proteins are implicated in cell growth and differentiation via regulation of mRNA expression in the cytoplasm. In human embryonic teratocarcinoma (hNT2) cells transfected with the human neuronal ELAV-like protein, Hel-N1, neurites formed, yet cells were not terminally differentiated. Cells in which neurite ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.13.4.449
更新日期：1999-02-15 00:00:00
abstract：:Cancer stem cells (CSCs) are postulated to be a small subset of tumor cells with tumor-initiating ability that shares features with normal tissue-specific stem cells. The origin of CSCs and the mechanisms underlying their genesis are poorly understood, and it is uncertain whether it is possible to obliterate CSCs with...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.171959.111
更新日期：2011-12-15 00:00:00
abstract：:A novel cysteine-rich motif, named LIM, has been identified in the homeo box genes lin-11, Isl-1, and mec-3; the mec-3 and lin-11 genes determine cell lineages in Caenorhabditis elegans. We isolated LIM class homeo box genes from Xenopus laevis that are closely related to lin-11 and mec-3 in the LIM and homeo domains....
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.6.3.356
更新日期：1992-03-01 00:00:00
abstract：:Proximal-distal outgrowth of the vertebrate limb bud is regulated by the apical ectodermal ridge (AER), which forms at an invariant position along the dorsal-ventral (D/V) axis of the embryo. We have studied the genetic and cellular events that regulate AER formation in the mouse. In contrast to implications from prev...
journal_title：Genes & development
pub_type： 杂志文章
doi：
更新日期：2000-06-01 00:00:00
abstract：:To define the functional pathways regulating epithelial cell migration, we performed a genome-wide RNAi screen using 55,000 pooled lentiviral shRNAs targeting ∼11,000 genes, selecting for transduced cells with increased motility. A stringent validation protocol generated a set of 31 genes representing diverse pathways...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1989110
更新日期：2010-12-01 00:00:00
abstract：:Persistent DNA double-strand breaks and telomeres represent genomic hazards, as they can instigate inappropriate repair reactions. Two recent papers by Oza and colleagues (pp. 912-917) and Schober and colleagues (pp. 928-938) show that both types of DNA ends are sequestered from bulk DNA by Mps3, a SUN domain protein ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1805309
更新日期：2009-05-01 00:00:00
abstract：:Wilms Tumor, the most common pediatric kidney cancer, evolves from the failure of terminal differentiation of the embryonic kidney. Here we show that overexpression of the heterochronic regulator Lin28 during kidney development in mice markedly expands nephrogenic progenitors by blocking their final wave of differenti...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.237149.113
更新日期：2014-05-01 00:00:00
abstract：:The reelin (reln) and disabled 1 (dab1) genes both ensure correct neuronal positioning during brain development. We have found that the intracellular Dab1 protein receives a tyrosine phosphorylation signal from extracellular Reln protein. Genetic analysis shows that reln function depends on dab1, and vice versa, as ex...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.13.6.643
更新日期：1999-03-15 00:00:00
abstract：:Genome instability is a recurring feature of tumorigenesis. Mutation in MLL2, encoding a histone methyltransferase, is a driver in numerous different cancer types, but the mechanism is unclear. Here, we present evidence that MLL2 mutation results in genome instability. Mouse cells in which MLL2 gene deletion can be in...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.275453.115
更新日期：2016-02-15 00:00:00
abstract：:The incorporation of histone H1 into chromatin during embryogenesis directs the specific repression of the Xenopus oocyte 5S rRNA genes. An increase in histone H1 content specifically restricts TFIIIA-activated transcription, and a decrease in histone H1 within chromatin facilitates the activation of the oocyte 5S rRN...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.8.10.1147
更新日期：1994-05-15 00:00:00
abstract：:The Agrobacterium Ti plasmid (T-DNA) 6b proteins interact with many different host proteins implicated in plant cell proliferation. Here, we show that Arabidopsis plants overexpressing 6b display microRNA (miRNA) deficiency by directly targeting SERRATE and AGO1 via a specific loop fragment (residues 40-55). In additi...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1985511
更新日期：2011-01-01 00:00:00
abstract：:The YAP transcription coactivator has been implicated as an oncogene and is amplified in human cancers. Recent studies have established that YAP is phosphorylated and inhibited by the Hippo tumor suppressor pathway. Here we demonstrate that the TEAD family transcription factors are essential in mediating YAP-dependent...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1664408
更新日期：2008-07-15 00:00:00
abstract：:Ecsit is a cytosolic adaptor protein essential for inflammatory response and embryonic development via the Toll-like and BMP (bone morphogenetic protein) signal transduction pathways, respectively. Here, we demonstrate a mitochondrial function for Ecsit (an evolutionary conserved signaling intermediate in Toll pathway...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.408407
更新日期：2007-03-01 00:00:00
abstract：:We identify the "M region" of the muscle-specific Xenopus cardiac actin gene promoter from -282 to -348 as necessary for the embryonic expression of a cardiac actin-beta-globin reporter gene injected into fertilized eggs. Four DNA-binding activities in embryo extracts, embryonic M-region factors 1-4 (EMF1-4), are desc...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.5.7.1149
更新日期：1991-07-01 00:00:00
abstract：:RNAi has revolutionized reverse genetics; however, RNAi is not necessarily ubiquitous or constitutive. Lund and colleagues (pp. 1121-1131) show that microRNA (miRNA) effector Argonautes (Agos) are limiting and easily saturated during early Xenopus embryogenesis. Moreover, this stage is devoid of slicing capacity. Supp...
journal_title：Genes & development
pub_type： 评论,杂志文章
doi：10.1101/gad.2062911
更新日期：2011-06-01 00:00:00
