Cell Science at a Glance 4249

SUMOylation and and this pathway has been implicated in SUMO-3. SUMO-2 and SUMO-3 are ~95%
controlling many aspects of cell physiology, identical to each other. In most contexts,
deSUMOylation at a including cell-cycle regulation, transcription, SUMO-2 and SUMO-3 cannot be distinguished,
glance nucleocytoplasmic transport, DNA replication and here we collectively refer to them as
and repair, chromosome dynamics, SUMO-2/3. SUMO-2 and SUMO-3 are each
Yonggang Wang and apoptosis, and ribosome biogenesis. ~45% identical to SUMO-1, and all mammalian
Mary Dasso* Both SUMOylation and deSUMOylation paralogues are ~ 45% identical to Smt3p.
Laboratory of Gene Regulation and Development, (SUMO deconjugation) are highly dynamic There are several important differences
National Institute of Child Health and Human processes. This poster article discusses the between the mammalian SUMO paralogues.
Development, Bethesda, MD 20892, USA
enzymes that mediate SUMOylation and First, some SUMO targets are conjugated only to
*Author for correspondence (mdasso@helix.nih.gov)
deSUMOylation, concentrating on their SUMO-1, others only to SUMO-2/3, and still
Journal of Cell Science 122, 4249-4252 mechanisms of action. Although it is not others to all SUMO paralogues (Vertegaal
Published by The Company of Biologists 2009
doi:10.1242/jcs.050542 possible to discuss individual SUMOylated et al., 2006). Second, the overall cellular
targets in detail, we will mention emerging concentration of SUMO-2/3 is greater than that of
paradigms that explain how SUMOylation SUMO-1, as is the pool of free protein available
Small ubiquitin-related modifiers (SUMOs) are might direct the fate of target proteins. for conjugation (Saitoh and Hinchey, 2000). It is
ubiquitin-like polypeptides that become thus likely that the bulk of SUMOylation
covalently conjugated to cellular proteins in a SUMO paralogues involves SUMO-2/3. Third, SUMO-1 and
manner similar to ubiquitylation (Johnson, Yeast express a single SUMO paralogue, called SUMO-2/3 show different subcellular
2004). More than 1000 proteins have been Smt3p in Saccharomyces cerevisiae. localization patterns (Ayaydin and Dasso, 2004;
identified as potential SUMO-conjugation Mammalian cells express three major SUMO Zhang et al., 2008). Fourth, photobleaching
(SUMOylation) targets (Hochstrasser, 2009), paralogues, called SUMO-1, SUMO-2 and experiments suggest that SUMO-1 is less
Journal of Cell Science

SUMOylation and DeSUMOylation at a Glance

jcs.biologists.org
Yonggang Wang and Mary Dasso

Key steps and components in the SUMO pathway SUMOylation confers multiple fates

S-1 a. Blocking a binding site

1. 2. 3. 4. 3.
Cleavage SUMO SUMO SUMOylation DeSUMOylation K
of SUMO activation transfer to of target (see below) Interactor
C-terminus (linkage to E2 enzyme (E3-dependent
Target Cell-cycle regulation
E1 enzyme) or -independent; SUMO-1 Interactor Gene transcription
see below) S Nucleocytoplasmic transport
E1, E2, E3 K K
SUMOylation
Target
T
Target DNA replication and repair
Ulp/SENP Target
arget
Aos1 Chromosome dynamics
SH DeSUMOylation
K
K Apoptosis
Uba2 SH Ubc9 Target S Ribosome biogenesis
Aos1 Target b. Creation of additional binding site
E3s Ulp/SENP Others
Ubc9

K K
S S Uba2 S S S S Target Target

Ulp/SENP AMP+PPi Aos1 SH Interactor

ATP Ulp/SENP Interactor
Uba2 SH Ubc9 SIM
SUMO-2/3 S-2/3 SIM S
K SUMOylation K
S E1, E2, E3
K Target Target S-2/3
Target DeSUMOylation S-2/3
T r e
S-2/3
Mammals S. cerevisiae S. pombe c. Conformation alteration g
a
Small ubiquitin-related modifiers SUMO-1, SUMO-2, SUMO-3 Smt3p Pmt3p
S S-2/3n
Activating enzyme (E1) Aos1 (Sae1)-Uba2 (Sae2) Aos1p-Uba2p Rad31p-Fub2p t
SUMO-2/3n K SUMOylation K
Ulp/SENP
Conjugating enzyme (E2) Ubc9 Ubc9p Hus5p E1, E2, E3 Target Target
SP-RING-type E3 ligases PIAS1, PIAS3, PIASxα (ARIP3), Siz1p (UII1p), Pli1p, Nse2p S-1 DeSUMOylation

PIASxβ (Miz1), PIASγ (PIAS4), Siz2p (Nfi1p),

K
Mms21 (Nse2) Mms21p
S-2/3
(Nse2p), Zip3p S-2/3
Un
IR E3 ligase RanBP2 (Nup358) K U
K U
Other E3 ligases HDAC4, KAP1, Pc2, Topors S-2/3n U Proteasome-mediated
S-2/3n
Ubiquitin degradation
Protease (Ulp/SENP) SENP1 (SuPr-2), SENP2 (SMT3IP2, UIp1p (Nib1p), Ulp1p, Ulp2p
Ulp/SENP E1, E2, STUbL Un S-2/3n
K K U S-2/3
SSP3, Axam2), SENP3 (SMT3IP1), Ulp2p (Smt4p)
Target Target U S-2/3
SENP5 (SMT3IP3), SENP6 (SSP1, U S-2/3
SUMO-1
SUSP1), SENP7 DUB K K
E1, E2, E3
Target

E3-dependent (Siz/PIAS-mediated) SUMOylation E3-independent (SIM-mediated) SUMOylation Mechanism of SUMO deconjugation by Ulp/SENP
NH2
K
Siz/ S Ulp/SENP S
c9 Gly O Gly
HS
Ub Target
9

O
PIAS
Ubc

O O S-Cys
Siz/ O Cys NH
c9 c9
S

NH
G

O
9
O

SGly Ub SGly
ly

PIAS S S
Ub S
Gly O
S Gly S
Ub
c S s
K K
S

O Cys Cys
NH Cys Gly Cy O
Target Ulp/SENP S
C

c9 Siz/ Siz/ S Ubc9 Target O Gly

ys

SGly SIM NH Gly S

S
Ub PIAS PIAS
NH2 K
SIM
K
S-Cys
Cys K SIM K NH2 K NH2 Target
NH2 Target Target Substrate Enzyme-bound substrate Thioester intermediate
SIM K NH2 Target
K Target (trans conformation) (cis conformation)
Target H2O
Target c9
Ub
HS
Cys S
O Gly

Ubc9-bound Free target Siz/PIAS and Ubc9- Conjugate Free target SIM-mediated Enzyme-bound Conjugate
OH Ulp/SENP S
O Gly
Ulp/SENP
SUMO bound substrate bound intermediate substrate HS-Cys OH HS-Cys

Free enzyme Product-bound enzyme

Abbreviations: DUB, deubiquitylating enzyme; E3s, E3 ligases; HDAC4, histone deacetylase 4; IR, internal repeat; KAP1,
KRAB-associated protein 1; Mms21, methyl methanesulfonate sensitivity protein 21; Pc2, polycomb group protein 2; PIAS,
protein inhibitor of activated STAT; RanBP2, Ran binding protein 2; S, SUMO; S-1, SUMO-1; S-2/3, SUMO-2/3; Sae1,
SUMO-activating enzyme subunit 1 (E1); Sae2, SUMO-activating enzyme subunit 2 (E1); SENP, sentrin-specific protease;
SIM, SUMO-interacting motif; Siz, SAP and Miz-finger domain-containing protein; SP-RING, Siz/PIAS RING-finger domain;
STUbL, SUMO-targeted ubiquitin ligase; SUMO, small ubiquitin-related modifier; Topors, topoisomerase I-binding RING
finger protein; U, ubiquitin; Ubc9, ubiquitin-conjugating enzyme E2 I (SUMO-conjugating enzyme); Ulp, ubiquitin-like-
protein-specific protease.
© Journal of Cell Science 2009 (122, pp. 4249-4252)

(See poster insert)

 4250 Journal of Cell Science 122 (23)
dynamic than the other SUMO paralogues, and
its pattern of conjugation responds differently to
heat shock and stress (Ayaydin and Dasso, 2004;
Saitoh and Hinchey, 2000).
Smt3p, SUMO-2 and SUMO-3 can form
conjugated chains through a single conserved
acceptor lysine (Bylebyl et al., 2003; Tatham
et al., 2001). SUMO-1 does not have an
equivalent lysine residue, and thus probably
does not act as a link in elongating chains
in vivo. However, SUMO-1 might terminate
chains that are elongated through serial
conjugation of SUMO-2/3 (Matic et al., 2008).
Notably, although SUMOylation does not seem
to rely upon the geometry of chain linkages to
confer information, as ubiquitylation does
(Pickart and Fushman, 2004), SUMO
conjugates built from different paralogues or
with different chain lengths can specify distinct
target fates, as discussed below.
SUMO-interacting motifs
SUMO-interacting motifs (SIMs) play a central
role in both the enzymology of the SUMO
Journal of Cell Science
pathway and in the fate of conjugated species.
The best-characterized class of SIM consists of a
hydrophobic core ([V/I]-x-[V/I]-[V/I]) flanked
by a cluster of negatively charged amino acids
(Kerscher, 2007). The SIM hydrophobic core
can bind to an interaction surface on SUMO
proteins in a parallel or antiparallel orientation.
The acidic residues adjacent to the core might
contribute to the affinity, orientation or
paralogue specificity of binding (Hecker et al.,
2006; Meulmeester et al., 2008). A variant SIM
was recently defined within the transcriptional
repressor CoREST1, consisting of [I/V/L]-
[D/E]-[I/V/L]-[D/E]-[I/V/L] with N-terminal
acidic residues (Ouyang et al., 2009). This SIM
is highly selective for SUMO-2/3 binding, and
differs from previously identified SIMs because
its core lacks a hydrophobic residue at position
4. Notably, the diversity of SIMs identified to
date is much less than the 16 known ubiquitin-
binding domains (Grabbe and Dikic, 2009); it is
reasonable to speculate that additional SIMs
remain to be discovered.
SUMO-processing, -activating and
-conjugating enzymes
Newly translated SUMO proteins are cleaved to
reveal C-terminal diglycine motifs. This
processing is mediated by a family of
proteases known as ubiquitin-like-protein-
specific proteases (Ulps) in yeast and
sentrin-specific proteases (SENPs) in mammals
(Mukhopadhyay and Dasso, 2007). Ulps and
SENPs also mediate deSUMOylation (see
below).
All SUMO paralogues share the same
activating (E1) and conjugating (E2) enzymes.
These enzymes are structurally similar to E1 and
E2 enzymes of ubiquitin, and they share many of
the properties that have been demonstrated for
those enzymes (Hochstrasser, 2009). The
yeast SUMO E1 enzyme is a heterodimer
consisting of Aos1p (also known as Sae1 in
vertebrates) and Uba2p (also known as Sae2
in vertebrates), which show sequence similarity
to the N-terminus and C-terminus of the
monomeric ubiquitin E1 enzyme, respectively
(Johnson et al., 1997). Aos1p-Uba2p catalyzes
the formation of a high-energy thioester bond
between Uba2p and the SUMO C-terminus,
with ATP hydrolysis to AMP and pyrophosphate
(Johnson et al., 1997; Lois and Lima, 2005). The
activated SUMO is subsequently passed to a
cysteine in the active site of the E2 enzyme,
Ubc9, through an intermolecular thiol-transfer
reaction.
Residues of Ubc9 that are directly involved in
the transfer of SUMO act to orient the lysine
of the target protein and to decrease its pKa,
resulting in a higher occurrence of its activated,
de-protonated state (Yunus and Lima, 2006).
SUMO transfer from Ubc9 to some target
proteins can occur through at least two ligase-
independent mechanisms. First, many
SUMOylated lysines lie within a consensus
motif, -K-x-[D/E] (where  is an aliphatic
branched amino acid and x is any amino acid).
Ubc9 can directly recognize this motif and
conjugate the lysine residue within it (Bernier-
Villamor et al., 2002). Second, some SUMO
substrates contain SIMs that promote their own
conjugation (Meulmeester et al., 2008; Zhu
et al., 2008). These SIMs bind to the SUMO
moiety to which Ubc9 is attached, thereby
increasing its local concentration and
facilitating SUMOylation. Because SIMs show
paralogue preference, this mechanism allows
targets to be modified in a paralogue-selective
manner. Notably, mammalian Ubc9 can itself be
SUMOylated on a nonconsensus lysine in its
N-terminal helix (Knipscheer et al., 2008). This
modification does not inhibit its activity per se,
but alters its target preference, increasing the
conjugation of substrates that contain SIMs,
which bind to the SUMO that is conjugated to
Ubc9.
SUMO ligases
SUMO ligases (E3 enzymes) facilitate the
majority of SUMOylation under physiological
conditions (Meulmeester et al., 2008). A number
of SUMO ligases have been described, most of
which seem to be specific to metazoans.
Siz/PIAS-family proteins
All eukaryotes express proteins with Siz/PIAS
RING-finger-like domains (SP-RING
domains), which are known as SAP and Miz-
finger domain (Siz) proteins in yeast and
protein inhibitor of activated STAT (PIAS)
proteins in vertebrates (Hochstrasser, 2001). In
budding yeast, Siz1p and Siz2p are required for
most Smt3p conjugation (Johnson and Gupta,
2001; Takahashi et al., 2001). Other SP-RING
proteins, Zip3p and Mms21p, promote
assembly of the synaptonemal complex
between homologous chromosomes during
meiosis (Cheng et al., 2006) and DNA repair
(Potts, 2009), respectively. The five vertebrate
PIAS proteins (PIAS1, PIAS3, PIASx,
PIASx and PIAS) have been implicated in
many processes, including gene expression,
signal transduction and genome maintenance
(Palvimo, 2007).
Beyond their SP-RING domains, Siz/PIAS-
family members share additional conserved
motifs, including an N-terminal scaffold
attachment factor (SAF)-A/B, acinus, PIAS
(SAP) motif, a PINIT motif, a SIM, and a
C-terminal domain that is rich in serine and
acidic amino acids (S/DE domain) (Palvimo,
2007). The SAP domain directs the localization
of Siz/PIAS proteins to chromatin within the
nucleus (Azuma et al., 2005; Palvimo, 2007).
Structural analysis of a Siz1 fragment that is
sufficient for E3 activity in vitro shows that it
has an elongated tripartite architecture, formed
by its N-terminal PINIT domain, SP-RING
domain and C-terminal domain, termed the
SP-CTD (Yunus and Lima, 2009). The SP-
RING and SP-CTD domains are required for
activation of the Ubc9-SUMO thioester,
whereas the PINIT domain directs
SUMOylation to the correct target lysine.
RanBP2
RanBP2 is a nuclear-pore protein that localizes
to the cytoplasmic face of the pore. RanBP2
possesses a domain called the internal repeat
(IR) domain, which consists of two tandemly
repeated sequences of around 50 residues (IR1
and IR2), separated by a 24-residue spacer (M).
RanBP2 fragments containing the IR domain
have SUMO ligase activity in vitro (Pichler
et al., 2002). Structural analysis of a RanBP2
fragment containing the IR1 and M domains
indicates that RanBP2 enhances Ubc9 activity
without direct contacts to the target protein
(Reverter and Lima, 2005). It has thus been
proposed that RanBP2 promotes SUMOylation
by aligning the Ubc9-SUMO thioester complex
in an optimal configuration for substrate
interaction with the active site of Ubc9 and for
catalysis. Notably, the IR domain of RanBP2
binds extremely stably to Ubc9 and the
SUMO-1-conjugated form of RanGAP1,
the activating protein for the GTPase Ran
(Matunis et al., 1998; Saitoh et al., 1998).
Structural analysis yielded the puzzling result

that this binding abolishes the ability of RanBP2
to promote multiple rounds of target
SUMOylation (Reverter and Lima, 2005). It
will clearly be important to establish how this
inhibition is overcome for RanBP2 to act as an
E3 enzyme in its physiological context.
Other SUMO ligases
Additional proteins that have been reported as
potential SUMO ligases include histone
deacetylase 4 (HDAC4), KRAB-associated
protein 1 (KPA1), Pc2 and Topors.
HDAC4 is a histone deacetylase that is a
SUMOylation target. HDAC4 expression
enhances the SUMOylation of myocyte-specific
enhancer factor 2 (MEF2), as well as other
targets (Geiss-Friedlander and Melchior, 2007;
Zhao et al., 2005). HDAC4 can bind to Ubc9,
suggesting that it acts as an E3 enzyme. It has
alternatively been proposed that HDAC4
enhances SUMOylation by other means, such
as promoting the phosphorylation of target
proteins at sites adjacent to conjugated lysine
residues (Yang and Gregoire, 2006).
Journal of Cell Science
The human co-repressor KRAB-associated
protein 1 (KAP1) possesses PHD-finger domains
that catalyze intramolecular SUMOylation of an
adjacent KAP1 bromodomain (Peng and
Wysocka, 2008). SUMOylation stabilizes the
association of the bromodomain with
the chromatin modifiers, thus promoting the
establishment of gene silencing. Structural
analysis suggests that the PHD finger and the
bromodomain cooperate as an integrated unit to
recruit Ubc9 and facilitate SUMOylation (Zeng
et al., 2008).
Mammalian Pc2 is a polycomb-group
protein that can act as a SUMO ligase for the
transcriptional co-repressor CtBP (Wotton and
Merrill, 2007). Pc2 can bind to both Ubc9 and its
conjugation targets, and it seems to have a rather
limited spectrum of targets.
Topors is a RING-finger protein that binds
DNA topoisomerase I and p53. It possesses both
RING-finger-dependent ubiquitin ligase
activity and RING-finger-independent SUMO
ligase activity (Weger et al., 2005). Topors has a
SIM (Hecker et al., 2006) and acts as a SUMO
ligase in vitro (Hammer et al., 2007).
SUMO-deconjugating enzymes
Ulps/SENPs are responsible both for processing
SUMO peptides and for deconjugating
SUMOylated species (Hay, 2007;
Mukhopadhyay and Dasso, 2007). Ulps/SENPs
share a conserved ~200-amino-acid catalytic
domain that is typically found near their
C-terminus.
There are two Ulps in budding yeast: Ulp1p
and Ulp2p (Li and Hochstrasser, 1999; Li and
Hochstrasser, 2000). Ulp1p localizes to the
Journal of Cell Science 122 (23)
nuclear envelope and is encoded by an
essential gene (Li and Hochstrasser, 1999).
Overexpression of processed Smt3p weakly
rescues ulp1 cells, but unprocessed Smt3p does
not (Li and Hochstrasser, 1999), suggesting that
one essential function of Ulp1p is Smt3p
maturation. Ulp2p localizes in the nucleoplasm
(Li and Hochstrasser, 2000) and is particularly
important for dismantling poly-Smt3p chains
(Bylebyl et al., 2003). Although not essential for
vegetative growth, Ulp2p has roles in
chromosome segregation, meiotic development
and recovery from cell-cycle checkpoint arrest
(Li and Hochstrasser, 2000).
Mammals have six SENPs: SENP1, SENP2,
SENP3, SENP5, SENP6 and SENP7. SENP1-3
and SENP5 are more similar to Ulp1p than to
Ulp2p, whereas SENP6 and SENP7 are more
Ulp2-like (Mukhopadhyay and Dasso, 2007).
SENP1 and SENP2 localize to the nuclear
envelope and have processing and
deconjugation activity for both SUMO-1 and
SUMO-2/3. By contrast, all other SENPs have a
strong preference for SUMO-2/3. SENP3 and
SENP5 localize in nucleoli and catalyze
SUMO-2/3 processing and deconjugation (Di
Bacco et al., 2006; Gong and Yeh, 2006).
Similar to Ulp1p (Panse et al., 2006), SENP3
and SENP5 have important roles in ribosome
biogenesis (Yun et al., 2008). SENP6 and
SENP7 localize within the nucleoplasm and are
implicated in the editing of poly-SUMO chains
(Lima and Reverter, 2008; Mukhopadhyay
et al., 2006; Shen et al., 2009).
The sites of SENP1, SENP2 and Ulp1p that are
engaged during processing or deconjugation are
shallow clefts lined with conserved amino acids
(Mossessova and Lima, 2000; Reverter and
Lima, 2004; Shen et al., 2006b). In both reactions,
the C-terminus of SUMO lies within these clefts
as an elongated strand, and conserved
tryptophans and other adjacent residues of Ulp1p,
SENP1 and SENP2 clamp the diglycine motif of
SUMO in a hydrophobic ‘tunnel’. During
deconjugation, such binding requires minimal
structural distortion of the target protein, which
explains how Ulps/SENPs can deconjugate many
SUMOylated species with only modest target
specificity. In the SUMO processing reaction,
Ulps/SENPs induce the isomerization of the
scissile peptide bond, resulting in a 90° kink in the
SUMO C-terminal tail (Reverter and Lima, 2006;
Shen et al., 2006a). In deconjugation reactions,
Ulps/SENPs induce the scissile isopeptide bond
between the C-terminus of SUMO and the
-amine group of the lysine residue of the target
protein to adopt a cis configuration, resulting in a
similar 90° kink (Reverter and Lima, 2006; Shen
et al., 2006a). For both peptide and amide bonds,
the kinked cis conformations facilitate hydrolysis
of the bond.
4251
The fates of SUMOylated species
The consequences of SUMOylation are diverse,
including alteration of the activity, localization
and/or stability of the target protein (Geiss-
Friedlander and Melchior, 2007). Frequently,
these consequences result from recognition of
conjugated species by SIM-containing proteins.
SUMOylation might also cause the loss of
binding partners, or cause conformational
changes that alter the enzymatic activity of the
target protein. Some SIM-mediated interactions
prevent deconjugation by limiting the access of
Ulps/SENPs to the conjugated proteins. In cases
in which the interacting SIMs have intrinsic
paralogue preference, they will selectively
protect targets that are modified with the
preferred SUMO paralogue (Zhu et al., 2009).
Few SUMOylation targets show quantitative
modification. Notably, SUMOylation can play
an important regulatory role even under these
circumstances (Geiss-Friedlander and Melchior,
2007). This might be explained by the
observation that SUMOylation can promote
the assembly of protein complexes, such as in
transcriptionally repressed chromatin, that
remain stable despite subsequent
deSUMOylation (Geiss-Friedlander and
Melchior, 2007). Additionally, SUMOylation
might function within the catalytic cycle of
targets, facilitating enzymatic turnover
(Hardeland et al., 2002). In both of these cases,
SUMOylated species are transient intermediates
that facilitate stable changes in target proteins.
Crosstalk between the SUMO and
ubiquitin pathways
A particularly exciting development in this field
has revealed an important point of crosstalk
between the SUMO and ubiquitin pathways
(Hunter and Sun, 2008): a subset of targets
become conjugated with multiple SUMOs, and
can be recognized by SUMO-targeted ubiquitin
ligases (STUbLs), causing the proteasomal
degradation of these targets. It is currently
believed that STUbLs operate primarily through
recognition of poly-SUMO chains, although it
remains possible that they might recognize some
targets that are mono-SUMOylated at numerous
sites.
Rfp1p and Rfp2p are fission-yeast RING-
finger proteins that possess N-terminal SIMs
(Sun et al., 2007). They are genetically
redundant and there is no visible phenotype for
loss of either gene encoding these proteins.
However, cells must possess at least one of these
proteins for growth and genome stability. Both
Rfp1p and Rfp2p heterodimerize with the Slx8p
protein, a RING-finger ubiquitin ligase.
Together, they mediate the ubiquitylation of
poly-SUMOylated targets, resulting in their
proteasomal destruction. The Slx5p-Slx8p
 4252 Journal of Cell Science 122 (23)
heterodimer acts similarly in budding yeast
(Hunter and Sun, 2008). The functions of Rfp1
and/or Rfp2 and Slx8 are performed by a single
protein in human cells, RING-finger protein 4
(RNF4), which is the only confirmed
mammalian STUbL (Sun et al., 2007).
Perspectives
Findings during the last 5 or 6 years have
provided a much more sophisticated
understanding of the SUMOylation pathway,
revealing some aspects that are unique to this
pathway and others that are probably common
to pathways involving all ubiquitin-like
proteins. However, the picture of SUMOylation
is not yet complete, and we expect that studies of
the SUMO pathway may yet hold more
surprises. In particular, we look forward to
future findings regarding the mechanisms of
SUMO ligases and the possibility that additional
SIMs remain to be discovered. Finally, we still
have much to learn regarding the biological
functions of this pathway and its interaction with
ubiquitin and other regulatory pathways.
Journal of Cell Science
This work was supported through Eunice Kennedy
Shriver National Institute of Child Health and Human
Development Intramural funds (Z01 HD001902).
Deposited in PMC for release after 12 months.
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