Abstract：
:Transcription is repressed if a DNA double-strand break (DSB) is introduced in close proximity to a transcriptional activation site at least in part by H2A-ubiquitination. While ATM signaling is involved, how it controls H2A-ubiquitination remains unclear. Here, we identify that, in response to DSBs, a transcriptional elongation factor, ENL (MLLT1), is phosphorylated by ATM at conserved SQ sites. This phosphorylation increases the interaction between ENL and the E3-ubiquitin-ligase complex of Polycomb Repressive Complex 1 (PRC1) via BMI1. This interaction promotes enrichment of PRC1 at transcription elongation sites near DSBs to ubiquitinate H2A leading to transcriptional repression. ENL SQ sites and BMI1 are necessary for KU70 accumulation at DSBs near active transcription sites and cellular resistance to DSBs. Our data suggest that ATM-dependent phosphorylation of ENL functions as switch from elongation to Polycomb-mediated repression to preserve genome integrity.
journal_name
Mol Celljournal_title
Molecular cellauthors
Ui A,Nagaura Y,Yasui Adoi
10.1016/j.molcel.2015.03.023subject
Has Abstractpub_date
2015-05-07 00:00:00pages
468-82issue
3eissn
1097-2765issn
1097-4164pii
S1097-2765(15)00214-2journal_volume
58pub_type
杂志文章相关文献
MOLECULAR CELL文献大全abstract：:Inappropriate activation of oncogenic kinases at intracellular locations is frequently observed in human cancers, but its effects on global signaling are incompletely understood. Here, we show that the oncogenic mutant of Flt3 (Flt3-ITD), when localized at the endoplasmic reticulum (ER), aberrantly activates STAT5 and...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2009.09.019
更新日期：2009-10-23 00:00:00
abstract：:Eukaryotic cells license far more origins than are actually used for DNA replication, thereby generating a large number of dormant origins. Accumulating evidence suggests that such origins play a role in chromosome stability and tumor suppression, though the underlying mechanism is largely unknown. Here, we show that ...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2011.02.006
更新日期：2011-03-04 00:00:00
abstract：:The ability to measure human aging from molecular profiles has practical implications in many fields, including disease prevention and treatment, forensics, and extension of life. Although chronological age has been linked to changes in DNA methylation, the methylome has not yet been used to measure and compare human ...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2012.10.016
更新日期：2013-01-24 00:00:00
abstract：:Metazoan histone mRNAs are unique: their pre-mRNAs contain no introns, and the mRNAs are not polyadenylated, ending instead in a conserved stem-loop structure. In Drosophila, canonical poly(A) signals are located downstream of the normal cleavage site of each histone gene and are utilized when histone 3' end formation...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2009.04.024
更新日期：2009-05-15 00:00:00
abstract：:Upon glucose restriction, eukaryotic cells upregulate oxidative metabolism to maintain homeostasis. Using genetic screens, we find that the mitochondrial serine hydroxymethyltransferase (SHMT2) is required for robust mitochondrial oxygen consumption and low glucose proliferation. SHMT2 catalyzes the first step in mito...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2018.01.024
更新日期：2018-02-15 00:00:00
abstract：:Loss of endogenous tumor suppression is a critical step on the road to cancer. In a recent paper in Molecular Cell, Wang and colleagues provide evidence that inactivation of the pivotal BRCA1 tumor suppressor disrupts a safeguard gene network that opposes cell proliferation and cell survival. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2008.10.007
更新日期：2008-10-24 00:00:00
abstract：:In eukaryotes, pre-mRNA exons are interrupted by large noncoding introns. Alternative selection of exons and nucleotide-exact removal of introns are performed by the spliceosome, a highly dynamic macromolecular machine. U4/U6.U5 tri-snRNP is the largest and most conserved building block of the spliceosome. By 3D elect...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2006.08.021
更新日期：2006-10-20 00:00:00
abstract：:Salmonella force their way into nonphagocytic host intestinal cells to initiate infection. Uptake is triggered by delivery into the target cell of bacterial effector proteins that stimulate cytoskeletal rearrangements and membrane ruffling. The Salmonella invasion protein A (SipA) effector is an actin binding protein ...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(04)00053-x
更新日期：2004-02-27 00:00:00
abstract：:The oncogenic process often leads to a loss of normal telomere length control, usually as a result of activation of telomerase. Nevertheless, there are also telomerase-independent events that involve a Rad50-dependent recombination mechanism to maintain telomere length. Previous work has implicated the Rb family of pr...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2006.02.016
更新日期：2006-04-07 00:00:00
abstract：:Type II topoisomerases are essential for resolving topologically entwined double-stranded DNA. Although anti-topoisomerase 2 (Top2) drugs are clinically important antibiotics and chemotherapies, to our knowledge, the mechanisms of cell killing by Top2 depletion and inactivation have never been directly compared. We sh...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2008.04.019
更新日期：2008-06-20 00:00:00
abstract：:Oocyte quality control culls eggs with defects in meiosis. In mouse, oocyte death can be triggered by defects in chromosome synapsis and recombination, which involve repair of DNA double-strand breaks (DSBs) between homologous chromosomes. We show that RNF212, a SUMO ligase required for crossing over, also mediates oo...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2018.08.031
更新日期：2018-10-18 00:00:00
abstract：:The transcriptional activity of many sequence-specific DNA binding proteins is directly regulated by posttranslational covalent modification. Although this form of regulation was first described nearly two decades ago, it remains poorly understood at a mechanistic level. The prototype for a transcription factor contro...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2005.08.013
更新日期：2005-10-07 00:00:00
abstract：:Reactive oxygen species (ROS)-induced activation of Apoptosis signal-regulating kinase 1 (ASK1) plays crucial roles in oxidative stress-mediated cell death through the activation of the JNK and p38 MAPK pathways. However, the regulatory mechanism of ASK1 in the oxidative stress response remains to be elucidated. Here,...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2012.09.018
更新日期：2012-12-14 00:00:00
abstract：:Heparan sulfate proteoglycans (HSPGs) influence the signaling of many growth factors, and recent work shows that they can promote VEGF signaling in trans from the surface of an adjacent cell. This mode of signaling also alters the activation state and internalization of VEGF receptors. ...
journal_title：Molecular cell
pub_type： 杂志文章,评审
doi：10.1016/j.molcel.2006.05.004
更新日期：2006-05-19 00:00:00
abstract：:Human sister chromatids at metaphase are primarily linked by centromeric cohesion, forming the iconic X shape. Premature loss of centromeric cohesion disrupts orderly mitotic progression. Shugoshin (Sgo1) binds to and protects cohesin at inner centromeres. The kinetochore kinase Bub1 phosphorylates histone H2A at T120...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2015.06.018
更新日期：2015-08-06 00:00:00
abstract：:Analysis of nuclear hormone receptor function in cells derived from xeroderma pigmentosum patients reveals novel links between DNA repair and transcription and points to novel mechanisms of regulating transcriptional regulators. ...
journal_title：Molecular cell
pub_type： 杂志文章,评审
doi：10.1016/s1097-2765(02)00511-7
更新日期：2002-04-01 00:00:00
abstract：:In the current issue of Molecular Cell, Liu et al. (2020) show that the secretion of cancer-linked forms of mutant calreticulin allow cancer cells to escape protective immune responses induced by chemotherapeutic and immunotherapeutic drugs, thereby promoting tumor growth. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2020.01.024
更新日期：2020-02-20 00:00:00
abstract：:The carboxy-terminal domain (CTD) of the large subunit of RNA polymerase II (Pol II) comprises multiple heptapeptide repeats of the consensus Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. Reversible phosphorylation of Ser2, Ser5, and Ser7 during the transcription cycle mediates the sequential recruitment of transcription/RNA pr...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2011.11.006
更新日期：2012-01-13 00:00:00
abstract：:Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins constitute an adaptive immune system in prokaryotes. The system preserves memories of prior infections by integrating short segments of foreign DNA, termed spacers, into the CRISPR array in a process termed adaptati...
journal_title：Molecular cell
pub_type： 杂志文章,评审
doi：10.1016/j.molcel.2016.01.030
更新日期：2016-03-17 00:00:00
abstract：:In this issue, Roberts et al. (2014) describe how hexokinase and mTORC1 cooperate to sense disequilibrium between glucose uptake and utilization and direct the balance of anabolism and catabolism to ensure the appropriate use of cellular resources. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2014.02.009
更新日期：2014-02-20 00:00:00
abstract：:In vitro, the anaphase-promoting complex (APC) E3 ligase functions with E2 ubiquitin-conjugating enzymes of the E2-C and Ubc4/5 families to ubiquitinate substrates. However, only the use of the E2-C family, notably UbcH10, is genetically well validated. Here, we biochemically demonstrate preferential use of UbcH10 by ...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2008.07.014
更新日期：2008-08-22 00:00:00
abstract：:During transcription initiation by bacterial RNA polymerase, the sigma subunit recognizes the -35 and -10 promoter elements; free sigma, however, does not bind DNA. We selected ssDNA aptamers that strongly and specifically bound free sigma(A) from Thermus aquaticus. A consensus sequence, GTA(C/T)AATGGGA, was required ...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2006.06.010
更新日期：2006-07-07 00:00:00
abstract：:The mechanisms controlling growth and patterning along the proximal-distal axis of the vertebrate limb are yet to be understood. We show that restriction of expression of the homeobox gene Meis2 to proximal regions of the limb bud is essential for limb development, since ectopic Meis2 severely disrupts limb outgrowth....
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(00)80393-7
更新日期：1999-11-01 00:00:00
abstract：:In solid tissues of vertebrates, initiation of mitochondrial DNA replication encompasses a broad zone downstream of the major noncoding region (NCR). In contrast, analysis with two-dimensional agarose gel electrophoresis of mitochondrial DNA replication intermediates in cultured human cells revealed initiation concent...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2005.05.002
更新日期：2005-06-10 00:00:00
abstract：:Given the intimate link between inflammation and dysregulated cell proliferation in cancer, we investigated cytokine-triggered gene expression in different cell cycle stages. Transcriptome analysis revealed that G1 release through cyclin-dependent kinase 6 (CDK6) and CDK4 primes and cooperates with the cytokine-driven...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2013.12.002
更新日期：2014-01-23 00:00:00
abstract：:Metformin has been reported to possess antitumor activity and maintain high cytotoxic T lymphocyte (CTL) immune surveillance. However, the functions and detailed mechanisms of metformin's role in cancer immunity are not fully understood. Here, we show that metformin increases CTL activity by reducing the stability and...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2018.07.030
更新日期：2018-08-16 00:00:00
abstract：:Nhp6A and Nhp6B are HMG1-like proteins required for the growth of S. cerevisiae at elevated temperatures. We show that the conditional lethality of an nhp6 strain results from defective transcription of SNR6 (U6 snRNA) by RNA polymerase III. Overexpression of U6 snRNA or Brf1, a limiting component of TFIIIB, and an ac...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(01)00179-4
更新日期：2001-02-01 00:00:00
abstract：:Using Micro-C, Hsieh et al. (2020) and Krietenstein et al. (2020) investigated 3D chromatin folding in human and mouse cells at unprecedented resolution to uncover ultra-fine-scale chromatin structures that provide direct links between genome architecture, gene expression, and gene regulation. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2020.04.021
更新日期：2020-05-07 00:00:00
abstract：:Heterochromatin formation is generally thought to result in transcriptional repression of target loci. However, RNAi-mediated heterochromatin assembly requires RNA polymerase II (Pol II) transcription. The mechanism facilitating Pol II accessibility to heterochromatin is unknown. We show that the fission yeast Epe1, a...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2006.05.010
更新日期：2006-06-09 00:00:00
abstract：:R loop, a transcription intermediate containing RNA:DNA hybrids and displaced single-stranded DNA (ssDNA), has emerged as a major source of genomic instability. RNaseH1, which cleaves the RNA in RNA:DNA hybrids, plays an important role in R loop suppression. Here we show that replication protein A (RPA), an ssDNA-bind...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2017.01.029
更新日期：2017-03-02 00:00:00
