449
288606074012055111
Title523185101344673106132202
MOLECULAR15031819018898177244318391471538611685
FUNCTIONS22151819018873153232306373416495574636
OF28781819018880153
THE30571819018867152226
CHROMATIN33101819018874159233312410483544587667
REMODELER40041819018873147245324403477544617691
FUN3047221819018874153232287342
Faculty5232097013453125196262288321385
Advisor9392097013481154215242290361396
Dr.15032093013875114133
Ahmed16702093013866128220278339
H.20432093013874108
Hassan21852093013874132181230288349
Al2569209301386691
Marzouqi26942093013885143183231290352412438
Defense5232328013477147178249315363433
Date9872328013477150183253
415032324013860
January15972324013846104165227285324379
201720102324013860121181241
Abstract7504237013481154202235271343414447
Many15032508013885143204258
studies1795250801384582143204229287336
have21622508013861119173230
identified2426250801382182140201238263293322380441
conserved29012508013847107168217275314369426487
ATP-dependent34192508013866124184224285343404462523584642703740
chromatin41932508013847108148207300357394419481
remodeling4708250801383693185245306364389414476536
complexes52792508013846106199259285342397453503
whose58122508013882143203252310
functions6156250801383191153204240265325387436
are1503263801385897155
to1692263801382988
modulate18072638013892152213274299357393451
DNA22852638013874148214
access25252638013858108159217266315
by28662638013861115
relieving3016263801383188114139197252277338399
chromatin-mediated34492638013843104144203295353390415476516609667727753810847905966
repression.4449263801383289150189247296345370430491524
We50002638013899153
have51792638013861119173230
previously54352638013861101158213238298359408433488
characterized59572638013843104162201257308345403442467516574635
Fun3015032768013857119180240300
in1838276801383091
Saccharomyces19642768013866124175225287344384443536589639697746
cerevisiae27452768013856114153211265291340365423480
as32602768013863112
a34062768013863
homodimer35042768013867126219278339364457515554
with40982768013882107144205
ATP-dependent43382768013871129189229290348409467528589647708745
chromatin51172768013856118157217309367404429490
remodeling56422768013844102194254315373398423484545
activity.62222768013863113150175230255292346370
Other15032898013878115176234273
studies1811289801385491152213238296345
have21902898013866124178235
shown24602898013853115175256318
that28122898013841103161197
Fun3030442898013862123185245305
plays3383289801386691149203252
a36692898013863
role37662898013845104129187
in3987289801383092
maintaining41182898013892150175236273331356417443504565
the47172898013842103161
silenced4912289801385479105162224275332393
state5340289801385390148185243
of56172898013865100
subtelomeric57512898013854115176213271296356448506546571621
and64072898013862124185
centromeric15033028013851109170207246306398456495521571
chromosomal21093028013851112152211303363412472564622647
regions.2791302801383997158183242304353386
Fun3032123028013857118180240300
has35463028013862120169
also3749302801385883132192
been39753028013861119177239
shown42483028013849111170252313
to4596302801383796
play4727302801386186144198
an49593028013858120
important51133028013825118178238278315372434470
role5618302801384099124182
in5834302801382687
DNA59563028013874148214
damage62043028013861119211269330388
repair1503315801384097158216241280
by18183158013871126
facilitating19783158013846102153178203228265323360385446507
long2520315801383595156217
range27723158013850105167228286
resection30923158013850107156214265302327387448
of35743158013871106
DNA37143158013885159225
in3973315801383697
Double41053158013885144206267292350
Strand44893158013872108148204265326
Breaks.48503158013875115172230285334367
This52523158013875136161210
thesis54973158013847108166215240289
was58213158013892149198
focuses60533158013846104155217266323372
on64603158013870132
understanding15033288013861123184241281330367425486547572633694
the2232328801383495153
mechanisms24173288013892150201262320381406455548597
by30483288013858113
which31933288013881143168218280
Fun3035073288013855116178238298
is3839328801382372
involved3945328801382284138196222276333394
in4374328801382284
DNA44893288013875148214
damage47383288013858115208266326384
repair.5157328801383794155212238277296
Results54843288013869125174235260297346
presented5865328801385897155204262323360418479
here63783288013859117156214
show15033418013849110170252
that18783418013846108165202
Fun3021153418013867128189250310
can24593418013860118180
anneal26733418013868129190248306331
complementary30393418013860120212273298356448506568604662702756
strands3830341801385996135191253313362
of42273418013869104
DNA43663418013884158224
that46243418013847108166202
is4861341801383584
facilitated49793418013845102152178203228265323359417478
by54923418013870125
ATP56513418013876134195
hydrolysis58803418013871125185225284309364413438487
and64023418013867129190
a15033548013858
helicase15953548013871129154179230288337395
activity20243548013868119155181235260297351
in2410354801383496
the25403548013847108166
presence27403548013871110168217275336387445
of32193548013870105
trap3358354801384786142203
DNA.35953548013885158224257
In38873548013850111
addition,40333548013867128189214251276336397430
Fun3044983548013867128190250310
was48423548013891148197
found50743548013844103164226287
to53953548013846106
be55363548013870128
able56983548013868129154212
to59443548013847106
relax60853548013849106132189244
both63633548013871131167229
negatively15033678013861119180238275300355411437491
and20293678013869130191
positively22553678013872132181206243268323380405460
supercoiled27493678013861122183241280331390416441499560
DNA33433678013886159225
in3603367801383698
an37353678013869131
ATP-independent39003678013878136196236261323384441502560622682740802838
manner47843678013893150212273331371
and51893678013869131191
cleave5415367801386287145203257314
a57633678013870
3’5867367801387195
overhang59963678013871125182222283341403463
in6494367801383698
a15033808013858
forked15953808013841100139194251312
DNA19413808013881154220
duplex21963808013866128189214272326
or25573808013865105
a26963808013864
duplex27943808013867128189214272327
that31553808013843104162199
has33883808013867125174
a35973808013863
protruding36953808013866106165202242303364389450511
3’.4241380801386589111
Annealing43873808013872133194252310335360422483
and49043808013863125186
3’5124380801386689
flap5248380801383564122182
endonuclease54653808013864125186246307368419444502560609667
activities61663808013864115151177231256293319376426
of1503393801386095
Fun3016323938013864125186246306
suggest19733938013855116177238296345382
a23893938013864
mechanism24933938013893151201263320382407456548
by30763938013867121
which32383938013881143168219280
Fun3035523938013864125186246307
can38933938013857114176
facilitates4103393801384198148174199224261319355413462
double46003938013867127188249274332
strand4966393801385592132188249310
break53103938013867107164222276
repair56213938013845103164221247286
by59423938013866121
the60973938013843105162
Single6294393801386792154215240298
Strand1503406801386198138194255316
Annealing18534068013879140202260317342368429490
pathway,23774068013874132168230311368422445
while28574068013894156181206264
a31554068013871
potential32604068013874134170228290326352409434
helicase37294068013874132157182233291340398
activity41614068013871121158183238263300354
can45504068013863121182
facilitate47674068013847104155180205230267325362420
Synthesis52214068013874127189226287345394419468
Depended57244068013887145206264325386444504
Strand62634068013874111150206268329
Annealing15034198013866127189247304330355416477
and20144198013870131192
as22404198013870119
a23934198013870
result24984198013851108157219244281
reduce28134198013852109170231282340
the31874198013849110168
generation33904198013872130192249289345382407467528
of39524198013872107
recombination40934198013852109160220312373398459517554579639700
intermediates.4828419801383798135193232325382443468526563621670703
Moreover,55664198013896156196253313367424463482
employing60834198013869162222248307361387448509
in1503432801382587
vivo1624432801387297152210
approaches,18694328013875136196236295353404465523572605
we25094328013898156
show27004328013866127187268
that30034328013854115173209
Fun3032474328013874136197257317
genetically35994328013877135197254291316367425450476530
interacts41644328013842103140198237293344381430
with46284328013899124161223
the48854328013854115173
Mus81509243280138102164213273333
nuclease54594328013879140191216274331381438
upon59324328013878139199260
chronic62274328013867129168227289314365
treatment1503445801383776134191228321378440477
with20164458013881107144205
chemicals22554458013853114172264290340398423472
that2762445801383899157194
stall2990445801385188146171196
the32214458013838100157
replication3413445801384199159185210260318355380440501
fork,3949445801383695135189223
suggesting42064458013851112173234292341377403464525
that47654458013839100158195
Fun3049944458013859120182242302
deletion53304458013863121146204240266325387
might57534458013892117178240276
lead6064445801382684142203
to6301445801383998
the64344458013838100158
accumulation15034588013858108159220313374399457494519579640
of21774588013866101
toxic23124588013842102156181231
recombination25784588013845102153213305366391453510547572632693
intermediates3306458801383092129186226318376437462520557615664
that40044588013843104162198
are42374588013863103160
difficult4432458801386691126156185236297322359
to48264588013842102
resolve49624588013845103152211237291348
in5345458801383192
the54714588013843104162
absence56674588013864124173231293343401
of61034588013865100
Mus81.62434588013885146195255315349
We15034718013899153
also1690471801385479128188
found1912471801383190151213274
that2220471801383394152188
Fun3024434718013853114176236296
deletion27694718013861119144202239264324385
affects3188471801385489123180231267317
the3539471801383394152
cell37254718013847105130156
cycle39154718013847101151177234
progression41804718013861100159220260317366415440500562
of4776471801385691
cells49014718013847104130155204
lacking5140471801382178129184209271331
TopI,55024718013864112173214247
without57804718013881107143205265326363
affecting6177471801385489123180231267292354415
the1503484801383798156
viability1693484801385883141201227252277314368
of2095484801386297
the22274848013839100158
cells.24204848013853111136161211244
This26984848013867128154203
might29374848013893118179240277
explain32484848013861115176201259284345
a36284848013860
function3722484801383898160210247272332393
for4150484801383796135
Fun3043204848013860121182242302
in4657484801382789
facilitating4780484801383894145170195220257315352377438499
the53144848013839100158
progression55074848013863102162223262319368418443502564
of6105484801386297
the62374848013839101158
cell64304848013853111136162
cycle15034978013851105155181238
in1776497801382688
the18984978013838100157
presence20904978013862102159208266327378436
of2560497801386297
torsional2691497801383898137186212271333391416
stress3141497801385087127184233282
which34594978013882143168219281
can37744978013852110171
be39804978013862120
induced4134497801382788149210261319379
by45484978013862117
TopI46994978013866114175216
deletion.49494978013862120146203240265325386420
Moreover,54044978013885145185242302356413452471
we59114978013881139
found6085497801383695156217278
that6398497801383899157194
Fun3015035108013857119180240300
is1838510801382069
not19375108013862121158
involved2130510801382082135194219274331392
in2556510801382182
removing2673510801383592185244299324385446
camptothecin31535108013846104197257294354391452510561586647
induced3835510801382082143204255312373
TopI/DNA42385108013864113174215257331405471
complexes47435108013846106199259285342397453502
since5280510801384570131182240
no55505108013861121
genetic57015108013860118180238274300350
interaction6086510801382082119176216272323359385444506
between15035238013861119155237295353414
Tdp119485238013864125186246
and22285238013854115176
Fun3024385238013853115176236296
was27655238013881138187
observed.29875238013855116165223263317374435469
Furthermore,34905238013853115154191252310350442502542599632
we41535238013881139
show43275238013845106166247
that4609523801383294152188
Fun3048325238013853114176236296
genetically51585238013861119180238275300351409434459514
interacts5706523801382283120178217273324361410
with61465238013882107144205
Asf163825238013866115150210
under15035368013861123184241281
DNA18165368013875148214
damaging20645368013859116209267327353414475
conditions,25735368013848108169230255292317377439488521
suggesting31285368013847108169230288337374399460521
that3683536801383596154190
Fun3039085368013855116178238298
is4240536801382372
required4346536801383795155217242282339400
in4780536801382384
the4899536801383495153
absence50865368013856117166224285336393
of5514536801385792
Asf1.56385368013866115150210244
Finally,5916536801385580141199224250304328
couple62795368013848107169230255313
of1503549901386095
models16685499013893153214272297346
are2048549901385999156
proposed22395499013861101160221281330388449
that2722549901383899157194
explain29865499013859113174199257282343
how33995499013863122204
Fun3036385499013858119181241301
annealing39735499013859120182240297322348409470
and44775499013859120181
nuclease46935499013862123174199257315364422
activities51495499013859110147172227252289314372421
may56055499013893151205
be58445499013862120
important59985499013826119180239279316374435472
in6504549901382688
the1503562901383798156
Single1689562901386187148209234292
Strand2011562901386198137193255316
Annealing23575629013866127188246304329354416477
pathway28645629013860118155216297354408
and33075629013853114175
how35125629013862121203
Fun3037495629013853115176236296
helicase40755629013862120145170221278327385
activity44955629013853104141166221246283336
might48625629013892117178239276
be51685629013861119
used53175629013861110168229
to5580562901383393
reduce5707562901383593154215266324
the6065562901383294152
level6251562901382179134191216
of6501562901385691
toxic1503575901383796150175226
recombination17635759013844101152212304365390451509546571631692
intermediates2490575901382990127185224317374435460518555613662
and31865759013862123184
thus34055759013840102163212
maintain36555759013893151176237274332357418
genomic41075759013865123184244337362412
stability,4554575901385390147208233259284321374398
which49905759013882143169219281
if5305575901382964
compromised54045759013854114207267307366459484533591652
could60905759013855114176201262
lead6386575901382987145206
to1503588901383796
cancer16345889013854112173224282321
or19905889013863103
other21275889013863100162219259
diseases.2420588901386590139197255304362411444
Dissertation4821614017098132193255344389431524566599689773
ZEINA6907710243100204260408556
SALIM13027710243104252340396576
AL-NATOUR193477102431482363204686167008689961112
Department6901010014684161240319358394506583655691
of14151010014677110
Biochemistry1559101001466998175252324401513542595631669739
and23321010014679151230
Molecular259610100146108184213290367439468547585
Biology3215101001466998175204281360429
College6901170014694170199228305384461
of11841170014677111
Medicine132811700146108185264293370399471548
and19091170014679151231
Heath21731170014682159238274346
Sciences25521170014663140168245317394471524