Abstract：
:When replication forks collapse, Rad3 phosphorylates the checkpoint-clamp protein Rad9 in a manner that depends on Thr 225, a residue within the PCNA-like domain. The physiological function of Thr 225-dependent Rad9 phosphorylation, however, remains elusive. Here, we show that Thr 225-dependent Rad9 phosphorylation by Rad3 regulates DNA repair pathways. A rad9(T225C) mutant induces a translesion synthesis (TLS)-dependent high spontaneous mutation rate and a hyper-recombination phenotype. Consistent with this, Rad9 coprecipitates with the post-replication repair protein Mms2. This interaction is dependent on Rad9 Thr 225 and is enhanced by DNA damage. Genetic analyses indicate that Thr 225-dependent Rad9 phosphorylation prevents inappropriate Rhp51-dependent recombination, potentially by redirecting the repair through a Pli1-mediated sumoylation pathway into the error-free branch of the Rhp6 repair pathway. Our findings reveal a new mechanism by which phosphorylation of Rad9 at Thr 225 regulates the choice of repair pathways for maintaining genomic integrity during the cell cycle.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Kai M,Furuya K,Paderi F,Carr AM,Wang TSdoi
10.1038/ncb1600subject
Has Abstractpub_date
2007-06-01 00:00:00pages
691-7issue
6eissn
1465-7392issn
1476-4679pii
ncb1600journal_volume
9pub_type
杂志文章abstract：:Changes in phosphorylation of the carboxy-terminal domain (CTD) of RNA polymerase II (RNAP) are associated with transcription initiation, elongation and termination. Sites of active transcription are generally characterized by hyperphosphorylated RNAP, particularly at Ser 2 residues, whereas inactive or poised genes m...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1663
更新日期：2007-12-01 00:00:00
abstract：:Micronucleation of missegregated chromatin can lead to substantial chromosome rearrangements via chromothripsis. However, the molecular details of micronucleus-based chromothripsis are still unclear. Now, an elegant system that specifically induces missegregation of the Y chromosome provides insight into this process,...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3458
更新日期：2016-12-23 00:00:00
abstract：:Cancer cells consume large quantities of glucose and primarily use glycolysis for ATP production, even in the presence of adequate oxygen. This metabolic signature (aerobic glycolysis or the Warburg effect) enables cancer cells to direct glucose to biosynthesis, supporting their rapid growth and proliferation. However...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2172
更新日期：2011-03-01 00:00:00
abstract：:Primordial germ cell (PGC) development in the human fetus remains relatively uncharted. A new study suggests that epigenetic reprogramming and sex differentiation in human PGCs occur asynchronously over an extended time period. This finding raises questions and implications for in vitro PGC differentiation. ...
journal_title：Nature cell biology
pub_type： 评论,杂志文章
doi：10.1038/ncb2665
更新日期：2013-01-01 00:00:00
abstract：:In the unicellular eukaryote Saccharomyces cerevisiae, Cln3-cyclin-dependent kinase activity enables Start, the irreversible commitment to the cell division cycle. However, the concentration of Cln3 has been paradoxically considered to remain constant during G1, due to the presumed scaling of its production rate with ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-019-0413-3
更新日期：2019-11-01 00:00:00
abstract：:During development, stem and progenitor cells gradually commit to differentiation pathways. Cell fate decisions are regulated by differentiation factors, which activate transcription programmes that specify lineage and differentiation status. Among these factors, the transforming growth factor (TGF)-beta family is imp...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb434
更新日期：2007-09-01 00:00:00
abstract：:Fetal haematopoietic stem cells (HSCs) self-renew extensively to build the blood system from scratch. The protein Lin28b negatively regulates the microRNA let-7 to keep levels of its target Hmga2 high, hence conferring high self-renewal potential to fetal HSCs. This regulatory circuit can be experimentally modulated t...
journal_title：Nature cell biology
pub_type： 评论,新闻
doi：10.1038/ncb2817
更新日期：2013-08-01 00:00:00
abstract：: ...
journal_title：Nature cell biology
pub_type： 评论,杂志文章
doi：10.1038/s41556-018-0246-5
更新日期：2018-12-01 00:00:00
abstract：:Symmetrical cell division requires duplication of DNA and protein content to generate two daughter cells. Centrosomes also duplicate during cell division, but the mechanism controlling this process is incompletely understood. We describe an alternative splice form of SadB encoding a short SADB Ser/Thr kinase whose act...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1921
更新日期：2009-09-01 00:00:00
abstract：:Glycogen has long been considered to have a function in energy metabolism. However, our recent study indicated that glycogen metabolism, directed by cytosolic phosphoenolpyruvate carboxykinase Pck1, controls the formation and maintenance of CD8+ memory T (Tmem) cells by regulating redox homeostasis1. This unusual meta...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-019-0440-0
更新日期：2020-01-01 00:00:00
abstract：:Proteins essential for vesicle formation by the Coat Protein I (COPI) complex are being identified, but less is known about the role of specific lipids. Brefeldin-A ADP-ribosylated substrate (BARS) functions in the fission step of COPI vesicle formation. Here, we show that BARS induces membrane curvature in cooperatio...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1774
更新日期：2008-10-01 00:00:00
abstract：:Vaccinia virus, a close relative of the causative agent of smallpox, exploits actin polymerization to enhance its cell-to-cell spread. We show that actin-based motility of vaccinia is initiated only at the plasma membrane and remains associated with it. There must therefore be another form of cytoplasmic viral transpo...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1101-992
更新日期：2001-11-01 00:00:00
abstract：:Inactivation of the von Hippel-Lindau (VHL) tumour-suppressor protein (pVHL) is associated with the von Hippel-Lindau cancer syndrome and the majority of kidney cancers. New evidence suggests that pVHL has properties of an F-box protein that targets the alpha-subunits of hypoxia-inducible factor (HIF)-1 for oxygen-dep...
journal_title：Nature cell biology
pub_type： 评论,新闻
doi：10.1038/35017129
更新日期：2000-07-01 00:00:00
abstract：:Nucleocytoplasmic transport occurs through nuclear pore complexes (NPCs) embedded in the nuclear envelope. Here, we discovered an unexpected role for yeast dynein light chain (Dyn2) in the NPC. Dyn2 is a previously undescribed nucleoporin that functions as molecular glue to dimerize and stabilize the Nup82-Nsp1-Nup159...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1604
更新日期：2007-07-01 00:00:00
abstract：:Actin dynamics is a tightly regulated process involved in various cellular events including biogenesis of clathrin-coated, AP-1 (adaptor protein 1)-coated transport carriers connecting the trans-Golgi network (TGN) and the endocytic pathway. However, the mechanisms coordinating coat assembly, membrane and actin remode...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2034
更新日期：2010-04-01 00:00:00
abstract：:Bcl-2 stimulates mutagenesis after the exposure of cells to DNA-damaging agents. However, the biological mechanisms of Bcl-2-mediated mutagenesis have remained largely obscure. Here we demonstrate that the Bcl-2-mediated suppression of hMSH2 expression results in a reduced cellular capacity to repair mismatches. The p...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1215
更新日期：2005-02-01 00:00:00
abstract：:Secretory proteins are transported to the Golgi complex in vesicles that bud from the endoplasmic reticulum. The cytoplasmic coat protein complex II (COPII) is responsible for cargo sorting and vesicle morphogenesis. COPII was first described in Saccharomyces cerevisiae, but its basic function is conserved throughout ...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/ncb2390
更新日期：2011-12-22 00:00:00
abstract：:The emergence of resistance to poly-ADP-ribose polymerase inhibitors (PARPi) poses a threat to the treatment of BRCA1 and BRCA2 (BRCA1/2)-deficient tumours. Stabilization of stalled DNA replication forks is a recently identified PARPi-resistance mechanism that promotes genomic stability in BRCA1/2-deficient cancers. D...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3626
更新日期：2017-11-01 00:00:00
abstract：:The formation of branched epithelial networks is fundamental to the development of many organs, such as the lung, the kidney or the vasculature. Little is known about the mechanisms that control cell rearrangements during tubulogenesis and regulate the size of individual tubes. Recent studies indicate that whereas the...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1049
更新日期：2003-10-01 00:00:00
abstract：:MAPKAP kinase 2 (MK2) is one of several kinases that are regulated through direct phosphorylation by p38 MAP kinase. By introducing a targeted mutation into the mouse MK2 gene, we have determined the physiological function of MK2 in vivo. Mice that lack MK2 show increased stress resistance and survive LPS-induced endo...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/10061
更新日期：1999-06-01 00:00:00
abstract：:Despite advances in the differentiation of insulin-producing cells from human embryonic stem cells, the generation of mature functional β cells in vitro has remained elusive. To accomplish this goal, we have developed cell culture conditions to closely mimic events occurring during pancreatic islet organogenesis and β...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-018-0271-4
更新日期：2019-02-01 00:00:00
abstract：:Chaperone proteins are thought to promote the correct folding and assembly of newly synthesized proteins and to facilitate restoration of the folded state under environmental conditions that favour protein denaturation. They are among the most ubiquitous and highly conserved of all proteins. The eukaryotic endoplasmic...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1001-891
更新日期：2001-10-01 00:00:00
abstract：:Centromeres are specialized chromosomal domains that direct kinetochore assembly during mitosis. CENP-A (centromere protein A), a histone H3-variant present exclusively in centromeric nucleosomes, is thought to function as an epigenetic mark that specifies centromere identity. Here we identify the essential centromere...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1899
更新日期：2009-07-01 00:00:00
abstract：:Although many genes that lead to different types of cancer when mutated have been identified, the cells that initiate tumour formation following accumulation of these mutations have, until recently, remained elusive. This review explores how mouse genetic lineage-tracing experiments that allow the expression of oncoge...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/ncb2657
更新日期：2013-02-01 00:00:00
abstract：:As obligatory intracellular parasites, viruses rely on host-cell functions for most aspects of their replication cycle. This is born out during entry, when most viruses that infect vertebrate and insect cells exploit the endocytic activities of the host cell to move into the cytoplasm. Viruses belonging to vaccinia, a...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/ncb0509-510
更新日期：2009-05-01 00:00:00
abstract：:Clathrin-coated vesicles (CCVs) are a central component of endocytosis and traffic between the trans-Golgi network (TGN) and endosomes. Although endocytic CCV formation is well characterized, much less is known about CCV formation at internal membranes. Here we describe two epsin amino-terminal homology (ENTH) domain-...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb901
更新日期：2003-01-01 00:00:00
abstract：:We have designed new non-peptidic potential inhibitors of gamma-secretase and examined their ability to prevent production of amyloid-beta 40 (Abeta40) and Abeta42 by human cells expressing wild-type and Swedish-mutant beta-amyloid precursor protein (betaAPP). Here we identify three such agents that markedly reduce re...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35074581
更新日期：2001-05-01 00:00:00
abstract：:Topoisomerase II (Topo II) is required to separate intertwined sister chromatids before chromosome segregation can occur in mitosis. However, it remains to be resolved whether Topo II has any role in checkpoint control. Here we report that when phosphorylated, Ser 1524 of Topo IIalpha acts as a binding site for the BR...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1828
更新日期：2009-02-01 00:00:00
abstract：:Starvation of animals or cells triggers autophagic degradation of cell contents to retrieve nutrients, but, paradoxically, mitochondria enlarge. This is now shown to result from inhibition of mitochondrial fission through PKA-mediated phosphorylation of the GTPase DRP1. Elongation of mitochondria optimizes ATP product...
journal_title：Nature cell biology
pub_type： 评论,新闻
doi：10.1038/ncb0511-521
更新日期：2011-05-01 00:00:00
abstract：:When cells enter mitosis with DNA that is unfit to be segregated, the consequences appear to be loss of centrosome function, abnormal spindles and a failure to segregate chromosomes. These defects may result from the workings of a surveillance mechanism that acts to cull irreparable nuclei. ...
journal_title：Nature cell biology
pub_type： 评论,新闻
doi：10.1038/35000099
更新日期：2000-02-01 00:00:00
