1
A compa ison be ween nuclea disman ling du ing plan and animal
p og ammed cell dea h
Fe nando Domínguez and F ancisco Ja ie Cejudo
Ins i u o de Bioquímica Vege al y Fo osín esis, Uni e sidad de Se illa and CSIC, A da
Amé ico Vespucio 49, 41092-Se illa, Spain
Co espondence o: F ancisco Ja ie Cejudo; Ins i u o de Bioquímica Vege al y
Fo osín esis, Uni e sidad de Se illa and CSIC, A da Amé ico Vespucio 49, 41092-
Se illa, Spain; E-mail: [email p o ec ed]
Key wo ds: apop osis, plan , p og ammed cell dea h, nuclease, nucleus disman ling
2
Abs ac
P og ammed cell dea h (PCD) is a p ocess o o ganized des uc ion o cells, essen ial
o he de elopmen and main enance o cellula homeos asis o mul icellula
o ganisms. Cells unde going PCD begin a degene a i e p ocess in esponse o in e nal
o ex e nal signals, whe eby he nucleus becomes one o he a ge s. The p ocess o
nucleus disman ling includes e en s a ec ing he nuclea en elope, such as o ma ion o
lobes a he nuclea su ace, selec i e p o eolysis o nucleopo ins and nuclea po e
complex clus e ing. In addi ion, ch oma in condensa ion inc eases in coo dina ion wi h
DNA agmen a ion. These p ocesses ha e been la gely s udied in animals, bu emain
poo ly unde s ood in plan s. The o e all p ocess o cell dea h has di e en
mo phological and biochemical ea u es in plan s and animals. Howe e , ecen
ad ances sugges ha nuclea disman ling in plan cells p og esses wi h mo phological
and biochemical cha ac e is ics simila o hose in apop o ic animal cells. In his e iew,
we summa ize nucleus disman ling in plan PCD, ocusing on he simila i ies and
di e ences wi h hei animal coun e pa s.
3
Con en s
1. In oduc ion
2. An o e iew o nuclea disman ling in animal cells
3. Simila i ies in nuclea disman ling in animal and plan cells unde going PCD
3.1. Signalling ha commi s nuclea disman ling in plan s
3.2. Sequence o e en s o plan nuclea disman ling du ing PCD
3.3. Nuclea disman ling is connec ed wi h cy oplasmic e en s du ing plan PCD
4. Is nuclea disman ling an au ophagic p ocess?
5. Concluding ema ks and u u e pe spec i es
Acknowledgemen s
Re e ences
4
1. In oduc ion
P og ammed cell dea h (PCD) is a p ocess o o ganized des uc ion o cells ha
main ains cellula homeos asis and is essen ial o he success ul de elopmen o
mul icellula o ganisms [1]. PCD is an impo an p ocess in plan s, as in o he
mul icellula o ganisms, no only o de elopmen [2], bu also as a mechanism o
immuni y agains pa hogen a ack [3]. Plan de elopmen al cell dea h a ec s o
de e mined cell ypes a p ecise s ages o de elopmen and is cha ac e ized by he
up u e o he acuola onoplas and subsequen elease o hyd olases, which deg ade
he cellula con en and, in some cases, he cell wall. Cell dea h in bio ic s ess depends
o he ype o pa hogens, bu ee adicals seem o exe an impo an unc ion [4].
The plan cell has peculia cha ac e is ics, mos no ably he p esence o he cell
wall and acuoles, which sugges ha he p ocess o PCD akes place wi h di e en
mo phological ea u es om apop osis o animal cells. Indeed, mos o he
mo phological ea u es o mammalian apop osis a e no ound in plan cells unde going
PCD and, hus, i has been p oposed ha cell dea h in plan s does no ake place by he
p ocess o apop osis; howe e , he deg ee o conse a ion o plan and animal cell dea h
p og ammes is a he momen a ma e o deba e [4]. The no ion ha plan s seem o
ha e e ol ed di e en mechanisms o PCD is ein o ced by he biochemical analyses
o he componen s in ol ed in he execu ion o cell dea h in di e en plan sys ems.
Despi e in ense sea ch, caspases ha e no been ound in plan s whe eas hey a e he
mos cha ac e is ic p o eases execu ing apop osis in animal cells. S ill, he e a e
caspase-like p o eases in ol ed in plan PCD [5]. Analyses ca ied ou in di e en plan
sys ems ha e iden i ied se e al ypes o p o eases in ol ed in cell dea h, which include
me acaspases [6], sub ilisin-like p o eases [7], and acuola p ocessing enzymes [8].
The e o e, bo h mo phological and biochemical cha ac e is ics sugges ha plan s and
animals ha e de eloped di e en s a egies ha pe o m cell dea h.
The s udy o PCD has been a majo ield o esea ch in di e en animal model
sys ems no only because i is an essen ial p ocess o unde s and de elopmen , bu also
because de egula ion o PCD causes al e a ions o he cellula homeos asis, which ha e
impo an implica ions associa ed wi h diseases, including cance o neu odegene a i e
p ocesses [9]. A he mo phological le el, animal PCD akes place by wo well-
es ablished mechanisms, apop osis and nec osis [10]. Apop osis is cha ac e ized by
ac i e plasma memb ane blebbing and cell agmen a ion, o ming he so-called
5
apop o ic bodies, which a e e en ually engul ed by phagocy es. In pa allel, he nucleus
unde goes d ama ic modi ica ions, which include diso ganiza ion o he nuclea
en elope, ch oma in condensa ion and in e nucleosomal deg ada ion o DNA in
agmen s o 180-200 bp and mul ime s o i , o ming a cha ac e is ic ladde , which
cons i u es a hallma k o apop osis [11]. In con as , nec osis is cha ac e ised by he
up u e o he plasma memb ane and he consequen deg ada ion o in acellula
con en s. Nec osis lacks he mo phological ea u es o apop osis, no ably he o ma ion
o apop o ic bodies. Inc easing a en ion has been de o ed o au ophagy, a p ocess o
cell sel -diges ion in which cellula componen s a e engul ed in esicles, called
au ophagosomes, p io o hei deg ada ion by lysosomes. I is well-es ablished ha
au ophagy has p o-dea h unc ions, bu his p ocess may also ha e p o-su i al
unc ions, and he ela ionship o au ophagy wi h apop osis is s ill he subjec o in ense
deba e [12].
The nucleus is he majo a ge o he cell deg ada ion machine y a he onse o
PCD. In apop o ic animal cells, he nucleus unde goes a massi e eo ganiza ion, which
includes he condensa ion o ch oma in and in e nucleosomal agmen a ion o DNA
[11]. Condensa ion o ch oma in has also been desc ibed in di e en plan sys ems. This
is he case o nuclei om nucella cells unde going PCD du ing whea g ain
de elopmen , he ch oma in o which condenses in a mo phologically simila manne as
occu s in apop o ic animal cells [13]. Simila ly, DNA ladde ing is also a hallma k o
PCD in di e en plan sys ems such as pea ca pel senescence [14]. Howe e , i should
be no ed ha bo h ch oma in condensa ion and DNA ladde ing a e no as consis en
PCD ma ke s in plan s as hey a e in animal cells. The e o e, despi e he clea
mo phological and biochemical di e ences o PCD in plan s and animals, he phase o
nuclea disman ling seems o ha e simila i ies in bo h ypes o cells. Indeed, ac o s
in ol ed in nuclea disman ling om plan cells a e able o induce apop o ic
mo phology and DNA agmen a ion in human cells [15], which sugges s he possibili y
o common mechanisms in PCD o cells om bo h kingdoms, a leas a he s age o
nucleus disman ling.
In his e iew, we will summa ize he cu en knowledge o he p ocess o
nuclea disman ling du ing PCD in plan sys ems, discussing he simila i ies and
di e ences wi h he p ocess in animal sys ems.
2. An o e iew o nuclea disman ling in animal cells

6
The con en o he nucleus, he nucleoplasm, is sepa a ed om he cy oplasm by
a complex memb anous nuclea en elope o med by ou e and inne nuclea
memb anes, which de ine he pe inuclea space. The nuclea en elope is pene a ed by
nuclea po e complexes ha media e he nucleo-cy oplasmic in e change in bo h
di ec ions [16]. The nuclea ma ix a he in e nal side o he nuclea en elope ac s as a
skele on de ining nuclea size and shape. Se e al nuclea memb ane p o eins localized
o he inne side o he nuclea en elope p o ide binding si es o ch oma in and nuclea
ma ix in animals and plan s. In animal cells he nuclea ma ix is composed o lamins
and lamin-associa ed p o eins [17], nuclei o plan cells lack his s uc u e, wi h sca old
and s uc u al suppo exe ed by coiled p o eins [18].
Mo phological and biochemical analyses ha e led o conside able ad ances o
ou knowledge o nuclea disman ling du ing animal apop osis [11]. The p o ein p o ile
o he nucleus in cells unde going apop osis is modi ied by he appea ance o
ansc ip ion ac o s, p o ein kinases, p o eases and DNases, among o he p o eins.
These p o eins a e p obably ansloca ed om he cy oplasm, as schema ically shown in
Figu e 1. One o he ea lies e en s aking place du ing nuclea disman ling is he
p o eolysis o ma ix a achmen egion-binding p o eins, which ancho ch oma in o he
sca old [19]. This limi ed clea age may open nuclease si es on he ch oma in s uc u e
allowing agmen a ion o DNA, which acili a es he subsequen p o eolysis o he bulk
o nuclea ma ix p o eins (Figu e 1). Se e al memb ane p o eins localized o he inne
side o he nuclea en elope, such as lamin B ecep o , lamin-associa ed polypep ide 2α
and nucleopo in Nup 153, a e connec ed o ch oma in. The clea age o hese p o eins
p omo es he de achmen o ch oma in om he nuclea en elope, which esul s in
nuclea po e clus e ing. Finally, i has been specula ed ha clea age o componen s o
he nuclea po e complex and he nuclea anspo machine y may s imula e an inc ease
in nuclea po e pe meabili y, acili a ing p o ein ansloca ion om he cy oplasm in o
he nucleus [19].
Pos - ansla ional modi ica ions o nuclea p o eins seem o ha e an impo an
unc ion in nuclea disman ling du ing apop osis. His ones H2, H3 and H4, lamins and
HMGA1a p o ein a e hype phospho yla ed, whe eas his one H1 is dephospho yla ed
jus be o e DNA agmen a ion [19]. I is wo h compa ing nuclea en elope
disassembly du ing mi osis and apop osis because diso ganiza ion o his s uc u e may
sha e common mechanisms in bo h p ocesses. Nup98, a pe iphe al nucleopo in
7
localized on bo h sides o he nuclea en elope, con ains 13 phospho yla ion si es ha
a e successi ely phospho yla ed by mi o ic kinases, d i ing nuclea po e complex
disassembly and nuclea en elope pe meabiliza ion du ing mi osis [20]. Hype -
phospho yla ion o Nup98 and o he nucleopo ins also seems o ha e a key egula o y
ole in apop osis. The pos - ansla ional modi ica ions o nuclea p o eins a e
p esumably impo an o h ee e en s: ch oma in condensa ion, accessibili y o
nucleases o DNA and he b eakdown o he lamina.
3. Simila i ies in nuclea disman ling in animal and plan cells unde going PCD
As men ioned abo e, animal cell nuclei unde go e y cha ac e is ic
mo phological changes du ing apop osis. The nucleus becomes agmen ed and he
agmen s mo e o apop o ic bodies, which a e subsequen ly phagocy osed by
mac ophages, pa enchymal o neoplas ic cells and deg aded by phagolysosomes [21].
The e o e, he nucleus o apop o ic animal cells becomes deg aded inside ano he cell.
In con as , in plan cells unde going PCD, he nucleus is no deg aded in ano he cell,
which is a clea di e ence o nuclea disman ling be ween plan and animal cell dea h.
Despi e hese di e ences, nuclea ex ac s o e opoxide-induced apop o ic
human cells igge ed apop o ic mo phology o plan cell nuclei [15]. In he same way
nuclea ex ac s om whea nucella cells unde going PCD induce apop o ic
mo phology and DNA agmen a ion in nuclei om human cells (Figu e 2). These
esul s sugges he exis ence o common mechanisms in he machine y o nuclea
disman ling in animal and plan cells.
CAD (Caspase Ac i a ed DNase) is he i s nuclease in apop o ic animal cells
esponsible o he cha ac e is ic in e nucleosomal deg ada ion o DNA [22]. CAD is
main ained in an inac i e s a us by he o ma ion o a complex wi h i s inhibi o [23].
The clea age o he inhibi o in apop o ic cells eleases ac i e CAD, hus allowing he
subsequen deg ada ion o DNA [24]. The inding ha nuclea ex ac s om plan cells
unde going PCD can igge apop o ic mo phology and DNA agmen a ion in nuclei
om human cells p omp ed us o sea ch o common elemen s o nuclea disman ling in
animal and plan cells. No candida e genes ha e been iden i ied so a encoding pu a i e
CAD o i s inhibi o in plan s. Apop osis-inducing ac o s ex ac ed om nuclei o plan
cells unde going PCD we e no inhibi ed by mammalian CAD inhibi o s (Figu e 2B).
Zn2+ and EDTA, inhibi o s o PCD- ela ed Ca2+ and/o Mg2+-dependen endonucleases
8
[15], inhibi ed he induc ion o animal apop osis (Figu e 2B). These esul s sugges ha
a CAD ype nuclease is no esponsible o DNA agmen a ion in plan cell nuclei
unde going PCD. The e o e nuclea disman ling in plan s seems o in ol e di e en
ac o s om hose in animals. Sea ch o plan homologues o he componen s o animal
cell apop osis has been ca ied ou by bioin o ma ic app oaches based on sequence
simila i y, which ha e no gi en posi i e esul s. The iden i ica ion o possible sha ed
genes will equi e sea ches based on s uc u e and unc ion a he han sequence.
3.1. Signalling ha commi s nuclea disman ling in plan s
The p ocess o PCD leading o nuclea disman ling can be schema ically
subdi ided in o h ee majo phases: signalling, execu ion and nuclea disman ling i sel .
The signalling and execu ion phases o PCD a e beyond he scope o his e iew. S ill,
some ecen ad ances in model plan sys ems, which sugges unc ional conse a ion o
key e en s egula ing PCD, a e he e discussed. The ice ansc ip ion ac o OsNAC4 is
ansloca ed in o he nucleus in a phospho yla ion-dependen manne in pa hogen-
igge ed hype sensi i e esponses. I ac i a es a Ca2+-dependen nuclease, which
p omo es nuclea DNA agmen a ion [25]. The me acaspase mcII-Pa is ansloca ed
om he cy oplasm o he nucleus du ing No way sp uce (Picea abies) emb yogenesis
and acili a es cell dea h by clea ing a phylogene ically conse ed nuclease [26, 27]. A
mi ogen-ac i a ed p o ein kinase appea s as a signalling ac o du ing ea ly PCD in
Papa e hoeas pollen, s imula ing DNA agmen a ion [28].
The pa hway o PCD culmina es in he p ocess o nuclea disman ling in bo h
plan and animal cells. As discussed abo e, he nuclei o plan and animal cells ha e
e y simila s uc u es and, despi e he di e ences, unde go simila modi ica ions, he
mos ele an being ch oma in condensa ion and DNA agmen a ion, in dying cells.
Thus he ques ion a ises whe he he key e en s o nuclea disman ling a e simila in
bo h ypes o cells. The mos ele an e en s aking place du ing nuclea disman ling in
animal and plan PCD a e summa ized in Table 1. The i s e en is he ansloca ion o
di e en ac o s and enzymes o he nucleus ha ini ia e he p ocess. In apop o ic animal
cells he mos ele an p ocess ha akes place a his s age is he ansloca ion o he
CAD complex wi h i s inhibi o [23, 24]. The ele an e en in plan s a his s age is he
ansloca ion o ansc ip ion ac o s, such as OsNAC4 [25], and he me acaspase mcII-
9
Pa [26]. Then, he ma u a ion o apop ogenic ac o s, o inac i a ion o hei inhibi o s,
occu s. The ele an ac i i y illus a ing his s age is he clea age o he inhibi o o
CAD by caspase-3 in animal cells unde going apop osis [24], and he clea age o he
Tudo S aphylococcal Nuclease (TSN) by me acaspase mcII-Pa [27] in plan PCD. The
dis up ion o he nucleo-cy oplasmic ba ie , acili a ed by limi ed diges ion o some
nucleopo ins o he nuclea po e complex, which al e s he pe meabili y h ough he
po e o an exclusion size o ca. 30 kDa o mo e han 70 kDa, has been documen ed in
apop o ic animal cells [29] bu , o ou knowledge, no in plan cells unde going PCD.
Simila ly, he p o ec ion om clea age o o he nucleopo ins un il he end o he dea h
p ocess has been documen ed only in apop o ic animal cells [30], bu no in plan cells.
A se ies o e en s ollows wi h he clea age o DNA in o di e en
con o ma ions (ch oma in loop DNA, oligonucleosomal DNA o naked DNA) ca alysed
by di e en nucleases. Examples o hese nucleases ha e been epo ed bo h in animal
and plan PCD (Table 1). Finally, nuclea po e complex clus e ing, which may acili a e
nuclea agmen a ion and ch oma in elease o he cy oplasm, as well as engul men o
nuclea agmen s, ha e also been epo ed in bo h ypes o cells [13, 19, 32, 36].
3.2. Sequence o e en s o plan nuclea disman ling du ing PCD
Two ypes o e en s can be dis inguished in he p ocess o nuclea disman ling;
hose a ec ing ch oma in s uc u e and DNA agmen a ion, and hose a ec ing he
nuclea en elope. The mos cha ac e is ic s uc u al ea u e in cells unde going PCD is
ha ch oma in becomes inc easingly condensed. This p ocess begins a he inne side o
he nuclea en elope, whe e disc e e pa ches o condensed ch oma in can be obse ed.
In animal cell apop osis he p og ession o ch oma in condensa ion can be classi ied in
h ee s ages: s age I, o ing condensa ion, s age II, o necklace condensa ion, and s age
III, o nuclea collapse/disassembly [37, 38], as schema ized in Figu e 3A. These s ages
a e less clea ly de ined in plan cells, bu he p ocess o ch oma in condensa ion
p og esses essen ially in he same way and culmina es in he o ma ion o disc e e
domains o condensed ch oma in [15, 26]. Two ypes o ch oma in condensa ion
mo phologies appea du ing pe al senescence: a) agmen s o condensed ch oma in
inside he nucleus and b) a la ge numbe o DNA sphe ical bodies, each en eloped by a
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19
Legends o igu es
Fig. 1. Key e en s o nuclea disman ling du ing apop osis. In animal cells he p ocess
o apop osis culmina es in nucleus disman ling. This p ocess equi es he ansloca ion
o p o eins om he cy oplasm o he nucleus, which p obably occu s in se e al wa es.
Some o he key e en s o nuclea disman ling a e he p o eolysis o nuclea ma ix and
nuclea en elope p o eins, allowing he de achmen o he nuclea en elope om he
ch oma in, he subsequen ch oma in condensa ion and he clus e ing o nuclea po e
complex. Clea age o nuclea po e complex p o eins p o okes he dis up ion o
nucleocy oplasmic ba ie , acili a ing he en ance o apop o ic ac o s. The p o eolysis
o ch oma in-associa ed p o eins close o he de achmen o he nuclea en elope may
open si es o nuclease hype sensi i i y p omo ing DNA agmen a ion by di e en
nucleases. P o ein phospho yla ion, along wi h o he pos - ansla ional modi ica ions, is
needed o acili a e nuclea ma ix dis up ion, ch oma in condensa ion and DNA
agmen a ion. Finally, nuclea agmen a ion is p oduced wi h he o ma ion o
apop o ic bodies and engul men by mac ophages.
Fig. 2. Ch oma in condensa ion and DNA agmen a ion in human cells can be
p omo ed by plan apop osis-inducing ac o s. A, HCT116 human cells we e ea ed
wi h nuclea ex ac s om whea nucella cells unde going PCD. Clea pa ches o
ch oma in condensa ion can be obse ed in he nucleus a e s aining wi h p opidium
iodide. B, DNA ex ac ed om hese cells was analysed in aga ose gels and s ained wi h
e hidium b omide. C, con ol un ea ed cells; +N, samples ea ed wi h nuclea ex ac s
om whea nucella cells unde going PCD, in he absence (-) o he p esence o pu i ied
Inhibi o o CAD (ICAD), Zn2+ o EDTA. This esul has no p e iously been epo ed,
de ails o expe imen al condi ions as p e iously desc ibed [19].
Fig. 3. The p oposed sequence o e en s o nuclea disman ling du ing plan PCD
in ol es ch oma in condensa ion, DNA agmen a ion and nuclea en elope dis up ion.
A, Fea u es o ch oma in condensa ion dis inguishing ing, necklace and
collapse/disassembly mo phologies [39]. B, P og essi e agmen a ion o DNA: high
molecula weigh DNA clea age, low molecula weigh DNA clea age and naked DNA
unspeci ic clea age. C, Nuclea en elope disassembly. Sequen ial clea age o plan
nucleopo ins Nup 93, Nup 96, Nup 214, Nup 50, Nup 62 and Tp /NUA was p oposed
20
based on apop o ic animal cells [30]. P o eolysis o plan lamin-like p o eins and Nup
136 nucleopo in was p oposed based on he simila ole o animal lamins and Nup 155,
al hough he e is no sequence homology.
21
Table 1
Rele an e en s in nuclea disman ling
E en
Examples and Re e ences
Animals
Plan s
T ansloca ion o he nucleus
CAD-Inhibi o complex [11, 23, 24]
T ansc ip ion ac o OsNAC4 [25]
Me acaspase mcII-Pa [26]
P ocessing o apop ogenics ac o s
o clea age o hei inhibi o s
Clea age o CAD inhibi o by caspase-3
[24]
Clea age o udo s aphylococcal nuclease
(TSN) by a me acaspase mcII-Pa [27]
Dis up ion o nucleocy oplasmic
ba ie
Deg ada ion o cy oplasmic ilamen s and
nuclea baske om nuclea po e complex
[29]
n.d.
P o ec ion o clea age si es o some
nucleopo ins
Nucleopo in Nup62 [30]
n.d.
Accessibili y o he con o ma ion o
DNA
- Ch oma in loops
Ch oma in loop nuclease [31]
Ch oma in loop nuclease [32]
- In e nucleosomal DNA
CAD nuclease [22, 23]
D-mannose-induced nuclease [33]
PCD- ela ed nuclease [15, 34]
- Naked DNA
Di e en nucleases [11]
ZEN1 nuclease [35]
Nuclea Po e Complex clus e ing
Nuclea Po e Complex clus e ing in
apop osis [19]
Nuclea Po e Complex clus e ing in plan
PCD [32]
Nuclea agmen engul men
Phagocy osis o apop o ic bodies by
mac ophages [36]
Au ophagic p ocess o emo e nuclea
agmen s [13, 32]
n.d.: no de e mined

22
Table 2
Sequence o cy oplasmic e en s p epa ing o plan nuclea disman ling
O ganelle
E en
Re e ences
ER-de i ed compa men s
Accumula ion and elease o cys eine p o eases and nucleases in
he onse o PCD
[41, 55]
ER-Golgi
Chape oning and inhibi ion o cys eine p o eases by p o ein
disul ide isome ase-5 du ing a icking o acuole be o e PCD
[56]
Vacuole (PSV and Ly ic
Vacuole)
-Sel -p ocessing o acuola p ocessing enzyme a acid pH
-Ma u a ion o p ecu so s o PR p o eins and hyd olases by
acuola p ocessing enzyme
-Accumula ion o aspa a e p o eases, cys eine p o eases and
nucleases un il hei elease in PCD
-Tonoplas dis up ion
[4, 57]
Mi ochond ia
Release o endonucleases, cy och ome c and o he apop ogenic
ac o s
[58]
Cho oplas
Release o ROS
[59]
Cy oskele on
Depolyme iza ion o mic o ubule and eo ganiza ion o ac in
ne wo k p o iding a skele on o igge au ophagosome
o ma ion and p omo ing au ophagic mo emen s o cell con en
engul men
[60]
Au ophagosomes and
au ophagic acuoles
Diges ion o emnan s o memb ane-less nuclea agmen s
[13, 32, 40]
23
Ea ly p o eolysis o
MAR-binding p o eins
De achmen o he nuclea
en elope om ch oma in
B eakdown o
nuclea ma ix
and en i e nucleus
P o eases
T ansc ip ion Fac o s
P o ein kinases
DNases
Inc ease/Modi ica ion in
nuclea po e pe meabili y
TRANSLOCATION
Nuclea Po e
Complex
clus e ing
P o eases
T ansc ip ion Fac o s
P o ein kinases
Dnases
P o eolysis o nuclea
memb ane and po e
p o eins
Ch oma in
condensa ion
Opened si es o
nuclease hype sensi i i y
DNA F agmen a ion
P
P
P
CYTOPLASM
NUCLEUS
Nuclea
En elope Nuclea
Ma ix Nuclea Po e
Complex P o eoly ic
e en PPhospho yla ionCh oma in
Figu e 1
24
2.0
1.0
0.6
0.4
0.2
kbp
C +N
-ICAD Zn EDTA
8.00 μm
A
B
Figu e 2
25
Nuclea
baske
ONM
INM
Nuclea
Ma ix
Cy oplasmic
ilamen s
Nup 93
Nup 96 Nup 62?
Nup 214
Nup 50
Lamin-like
p o eins
Tp /NUA
Nup 136
S age I
Necklace
condensa ion
Ring pe iphe al
condensa ion Collapse
condensa ion
S age II S age III
50 kpb Loop
DNases
30 nm DNA
ilamen “Beads on a s ing”
DNA ilamen
In e nucleosomal
DNases
Caspase-like
p o eases
O he p o eases
180 bp oligome s
DNA ilamen s
DNA
smea
“Naked” DNA
ilamen s
Unspeci ic
DNases
50 kbp oligome s
DNA ilamen
A Ch oma in Condensa ion
B DNA F agmen a ion
C Nuclea En elope / Nuclea Po e Disassembly
Figu e 3