September 2009 Volume 16 Number 9, pp 899 - 1001
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Nature Reviews Molecular Cell Biology
Focus on Endocytosis
September 2009
Endocytic membrane trafficking involves the cellular internalization
and sorting of extracellular molecules, plasma membrane proteins and
lipids. Endocytosis is required for a vast number of functions,
including nutrient uptake, cell adhesion and migration, receptor
signalling, pathogen entry and cell polarity.
This special Focus reflects the diversity and complexity of endocytic
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EDITORIAL
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The unsung reviewer p899
Manuscript peer reviewing is at the heart of the scientific system,
but it seems that these duties are often not properly (if at all)
recognized by universities, funding agencies or even the rest of the
scientific community.
doi:10.1038/nsmb0909-899
http://links.ealert.nature.com/ctt?kn=101&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
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NEWS AND VIEWS
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The p53 transcriptional synapse: activation on demand pp900 - 901
The adequate and on-time response of cellular transcription to
internal needs and external stimuli is a delicate task. Is the
transcriptional regulator p53 on call to permit rapid activation
of its target genes? A new study reports interplay of p53 with a
previously unidentified regulator, calcineurin-binding protein 1
(Cabin1), and provides evidence for such a mechanism.
Genrich V Tolstonog and Wolfgang Deppert
doi:10.1038/nsmb0909-900
http://links.ealert.nature.com/ctt?kn=11&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
When chromatin meets splicing pp902 - 903
Using bioinformatics analysis of previously published global genome
deep-sequencing data, two papers now show that DNA sequences
associated with nucleosomes are preferentially located in exons.
The correlation between nucleosome distribution and the exon-intron
organization of genes may have a key role in exon recognition at the
pre-mRNA level during co-transcriptional splicing, consistent with
previous findings indicating chromatin-mediated regulation of
alternative splicing.
Alberto R Kornblihtt, Ignacio E Schor, Mariano Allo and Benjamin J
Blencowe
doi:10.1038/nsmb0909-902
http://links.ealert.nature.com/ctt?kn=14&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
New functions for an ancient domain pp904 - 907
Macrodomains function as binding modules for metabolites of NAD+,
including poly(ADP-ribose). Three new studies explore how binding
of poly(ADP-ribose) by the macrodomains of histone variant
macroH2A1.1 and the ATP-dependent chromatin-remodeling protein ALC1
(also called CHD1L) leads to the modulation of chromatin structure,
regulating nuclear functions such as DNA-damage detection and repair.
W Lee Kraus
doi:10.1038/nsmb0909-904
http://links.ealert.nature.com/ctt?kn=18&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Dangerous play[mdash]splitting the message may leave you empty
handed pp907 - 908
An important aspect of eukaryotic gene expression is the efficient
integration of transcription, pre-mRNA processing and nuclear export.
A new study demonstrates that pre-mRNA transcript continuity is an
essential component for maintaining productive coupling of
transcription and RNA processing events.
Yvonne Klaue and Klemens J Hertel
doi:10.1038/nsmb0909-907
http://links.ealert.nature.com/ctt?kn=115&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
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RESEARCH HIGHLIGHTS
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Research highlights p909
doi:10.1038/nsmb0909-909
http://links.ealert.nature.com/ctt?kn=109&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
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ARTICLES
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Cabin1 restrains p53 activity on chromatin pp910 - 915
The tumor suppressor p53 activates the transcription of a number of
genes under conditions of genotoxic stress. Some of these regulated
promoters show p53 occupancy even under normal conditions. Now
calcineurin-binding protein 1 (Cabin1) is shown to keep p53 inactive
in these promoters.
Hyonchol Jang, Soo-Youn Choi, Eun-Jung Cho and Hong-Duk Youn
doi:10.1038/nsmb.1657
Abstract: http://links.ealert.nature.com/ctt?kn=73&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=13&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Fast ribozyme cleavage releases transcripts from RNA polymerase II
and aborts co-transcriptional pre-mRNA processing pp916 - 922
Co-transcriptional splicing of pre-mRNAs has been proposed to involve
exon tethering to the elongating RNA polymerase II. By inserting a
fast-cleaving ribozyme in the nascent transcript, the linear
integrity of the transcript is found to be key to splicing, arguing
against tethering and for a pathway that clears such disrupted
transcripts.
Nova Fong, Marie Ohman and David L Bentley
doi:10.1038/nsmb.1652
Abstract: http://links.ealert.nature.com/ctt?kn=67&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=108&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
A macrodomain-containing histone rearranges chromatin upon sensing
PARP1 activation pp923 - 929
Phosphorylation-dependent SUMOylation of MEF2A promotes postsynaptic
dendrite differentiation. Analyses now reveal that a surface on the
SUMO E2 UBC9 is responsible for integrating phosphorylation signal
recognition and SUMOylation and suggests that regulation of some
SUMO substrate recognition events may have evolved to use the E2
rather than an E3 ligase.
Gyula Timinszky et al.
doi:10.1038/nsmb.1664
Abstract: http://links.ealert.nature.com/ctt?kn=69&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=113&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
The molecular basis for the regulation of the cap-binding complex by
the importins pp930 - 937
The cap binding complex (CBC) interacts with mRNAs and snRNAs and
accompanies them to the cytoplasm, where they are released and CBC
is imported back into the nucleus by the importin complex. Multiple
approaches are now combined to gain structural and functional
insights into the regulation and coordination of these CBC
interactions.
Sandra M G Dias et al.
doi:10.1038/nsmb.1649
Abstract: http://links.ealert.nature.com/ctt?kn=80&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=92&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Dynamics and function of compact nucleosome arrays pp938 - 944
Nucleosomes can interfere with DNA binding by factors, but previous
work showed that protein-binding sites on a single nucleosome are
accessible. Dynamics in the context of higher-order chromatin
structure are now examined, with compaction dynamics and DNA-binding
site exposure on a centrally placed nucleosome in an array assessed.
Michael G Poirier, Eugene Oh, Hannah S Tims and Jonathan Widom
doi:10.1038/nsmb.1650
Abstract: http://links.ealert.nature.com/ctt?kn=83&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=91&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
A molecular basis for phosphorylation-dependent SUMO conjugation by
the E2 UBC9 pp945 - 952
Phosphorylation-dependent SUMOylation of MEF2A promotes postsynaptic
dendrite differentiation. Analyses now reveal that a surface on the
SUMO E2 UBC9 is responsible for integrating phosphorylation signal
recognition and SUMOylation and suggests that regulation of some
SUMO substrate recognition events may have evolved to use the E2
rather than an E3 ligase.
Firaz Mohideen et al.
doi:10.1038/nsmb.1648
Abstract: http://links.ealert.nature.com/ctt?kn=75&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=65&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Structural determinants of miRNAs for RISC loading and
slicer-independent unwinding pp953 - 960
miRNAs are loaded onto Argonautes (Agos) to guide silencing of
targets, but duplex unwinding is required for targeting. Detection
of Drosophila Ago1 complexes containing the duplexed or unwound miRNA
now give insight into the basis for cleavage-independent unwinding of
miRNA duplexes to generate a functional, mature complex.
Tomoko Kawamata, Herve Seitz and Yukihide Tomari
doi:10.1038/nsmb.1630
Abstract: http://links.ealert.nature.com/ctt?kn=31&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=71&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Existence of a microRNA pathway in anucleate platelets pp961 - 966
Platelets are anucleate elements in the cardiovascular system
involved in clotting. Platelets are now found to contain microRNAs
and the key cytoplasmic elements of a processing and effector pathway,
suggesting that platelet mRNAs may be subjected to microRNA regulation.
Patricia Landry et al.
doi:10.1038/nsmb.1651
Abstract: http://links.ealert.nature.com/ctt?kn=33&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=78&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Template strand scrunching during DNA gap repair synthesis by human
polymerase lambda pp967 - 972
X family DNA polymerases can fill short DNA gaps by binding both the
5prime and 3prime ends of the gap. What happens to the template strand
is now revealed in the crystal structure of human polymerase lambda
bound to a 2-nucleotide gap substrate. The template strand is
scrunched, with the additional base in an extrahelical position going
into an enzyme pocket.
Miguel Garcia-Diaz et al.
doi:10.1038/nsmb.1654
Abstract: http://links.ealert.nature.com/ctt?kn=36&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=56&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Molecular mechanisms for protein-encoded inheritance pp973 - 978
Prions can adopt a transmissible beta-sheet-rich conformation and
also form strains with different structural and biological properties.
Polymorphic crystal structures of peptides from prion- and other
amyloid-forming proteins suggest the structural basis for prion
strains, revealing two potential mechanisms: packing and segmental
polymorphism.
Jed J W Wiltzius et al.
doi:10.1038/nsmb.1643
Abstract: http://links.ealert.nature.com/ctt?kn=38&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=46&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Structural basis of high-fidelity DNA synthesis by yeast DNA
polymerase delta pp979 - 986
DNA polymerase delta (Pol delta) has a crucial role in eukaryotic
replication. Now the crystal structure of the yeast DNA Pol delta
catalytic subunit in complex with template primer and incoming
nucleotide is presented at 2.0-A resolution, providing insight into
its high fidelity and a framework to understand the effects of
mutations involved in tumorigenesis.
Michael K Swan et al.
doi:10.1038/nsmb.1663
Abstract: http://links.ealert.nature.com/ctt?kn=40&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=43&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
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BRIEF COMMUNICATION
----------------------
Insights into anaphase promoting complex TPR subdomain assembly from
a CDC26-APC6 structure pp987 - 989
The anaphase promoting complex (APC) is a key cell-cycle regulator
that has ubiquitin-ligase activity. The first structure of a complex
formed between APC subunits, that of CDC26 and APC6, provides
detailed structural information of APC components and suggests how
CDC26 may stabilize APC6 and other complex subunits.
Jing Wang et al.
doi:10.1038/nsmb.1645
Abstract: http://links.ealert.nature.com/ctt?kn=42&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=49&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
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ANALYSES
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Chromatin organization marks exon-intron structure pp990 - 995
Schraga Schwartz, Eran Meshorer and Gil Ast
doi:10.1038/nsmb.1659
Abstract: http://links.ealert.nature.com/ctt?kn=44&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=16&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Nucleosome positioning as a determinant of exon recognition
pp996 - 1001
Hagen Tilgner et al.
doi:10.1038/nsmb.1658
Abstract: http://links.ealert.nature.com/ctt?kn=47&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=17&m=33987209&r=MTc2OTcxOTY5MQS2&b=2&j=NTc1Mzg0ODcS1&mt=1&rt=0
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