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(Drosophila) Tj
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[ (embryo\056 Finally) 74 (\054 the ) ] TJ
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(Drosophila) Tj
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[ (KEY) 18 ( WORDS\072 Xeroderma pigmentosum\054 Cell cycle) ] TJ
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[ (INTR) 17 (ODUCTION) ] TJ
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0.005 Tc
0.0002 Tw
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T*
[ (exposure and cutaneous abnormalities\056 Among eight XP) 37 ( causative) ] TJ
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T*
(genes\054 ) Tj
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(XPB ) Tj
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[ (al\056\054 2010\073 Egly and Coin\054 201) 37 (1\051\056 Mutations in the human ) ] TJ
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(2) Tj
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(3) Tj
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[ (Depar) -63 (tment) ] TJ
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(4) Tj
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(Institute of) Tj
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[ (T) 19 (his is an Open Access ar) -63 (tic) 19 (le distrib) 10 (uted under the ter) -36 (ms of) -117 ( the Crea) 10 (tiv) 37 (e Commons) ] TJ
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[ (Attrib) 10 (ution License \050http\072\057\057crea) 10 (tiv) 37 (ecommons) 37 (\056org\057licenses\057b) 19 (y\0573\0560\051\054 w) -27 (hic) 10 (h per) -36 (mits unrestricted) ] TJ
T*
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0 Tw
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(Received 14 May 2014\073 Accepted 5 November 2014) Tj
ET
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BT
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[ (XP) 37 ( \050XP\057CS\051 in XP\055D patients ) ] TJ
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[ (\050Fig\056) -309 (1) ] TJ
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(A\073 supplementary material) Tj
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[ (T) 70 (able S1\073 Fan et al\056\054 2008\073 Lehmann\054 2001\051\056 XP) 37 ( mutations cause a) ] TJ
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T*
(2000\05510\054000\055fold increase in skin cancer risk\054 and some XP) Tj
0.0081 Tc
0.04691 Tw
T*
(patients also display primary neuronal degeneration \050Bradford et) Tj
0.015 Tc
0.35699 Tw
T*
[ (al\056\054 201) 37 (1\051\056 TTD patients display developmental retardation\054) ] TJ
0.00571 Tc
0.0493 Tw
T*
(neurological abnormalities due to dysmyelination\054 and some also) Tj
0.0108 Tc
0.0442 Tw
T*
[ (have photosensitivity) 65 (\054 but they do seem not to be predisposed to) ] TJ
-0.0033 Tc
0.0083 Tw
T*
[ (developing skin cancer \050Hashimoto and Egly) 65 (\054 2009\073 Ber) 18 (gmann and) ] TJ
0.01289 Tc
0.0421 Tw
T*
[ (Egly) 65 (\054 2001\051\056 TTD mutations seem to primarily cause a defect in) ] TJ
0.015 Tc
0.2692 Tw
T*
(the transcription function of TFIIH\054 and the severity of the) Tj
0.37801 Tw
T*
(transcriptional defects parallels the severity of the clinical) Tj
0.00771 Tc
0.0473 Tw
T*
[ (phenotype of TTD patients \050Bernebur) 18 (g and Lehmann\054 2001\051\056 CS) ] TJ
0.015 Tc
0.16299 Tw
T*
(seems to be caused by a defect in transcription\055coupled NER) Tj
0.0076 Tc
0.04739 Tw
T*
(\050Marteijn et al\056\054 2014\051\054 causing transcriptional stress\054 accelerated) Tj
0.015 Tc
0.26089 Tw
T*
[ (aging and cell death\056 CS also causes severe sun sensitivity) 65 (\054) ] TJ
-0.0031 Tc
0.0081 Tw
T*
(premature aging and severe developmental defects such as reduced) Tj
-0.0041 Tc
0.00909 Tw
T*
(body size\054 skeletal abnormalities and eye problems \050Kraemer et al\056\054) Tj
0.015 Tc
0.38029 Tw
T*
(2007\073 Laugel\054 2013\051\056 Furthermore\054 XP\055D mutations of the) Tj
0.27049 Tw
T*
(combined XP\057CS type have been described to uncouple the) Tj
0.0114 Tc
0.04359 Tw
T*
[ (incision process from the DNA) 55 ( damage \050Bernebur) 18 (g et al\056\054 2000\051) ] TJ
-0.0036 Tc
0.00861 Tw
T*
[ (and to cause UV) 92 (\055induced strand displacement \050Godon et al\056\054 2012\051\056) ] TJ
0.005 Tc
0.2442 Tw
0.947 -1.158 Td
[ (DNA) 55 ( is under constant attack and needs to be repaired\054 in) ] TJ
0.06979 Tw
-0.947 -1.158 Td
(particular when exposed to mutagenic agents\056 NER is one of the) Tj
-0.00681 Tc
0.0018 Tw
T*
(pathways that repairs helix\055distorting lesions\054 which can be induced) Tj
0.005 Tc
0.0414 Tw
T*
[ (by chemical agents or UV) 129 (\054 and it depends on TFIIH components\054) ] TJ
-0.005 Tc
0.03729 Tw
T*
(including XPD \050Lehmann\054 2003\051\056 The role of XPD in NER is well) Tj
0.0085 Tw
T*
(established\073 it acts as a component of TFIIH and unwinds the DNA) Tj
0.005 Tc
0.0473 Tw
T*
[ (at the site of damage \050Coin et al\056\054 2007\051\056 Its A) 111 (TPase and helicase) ] TJ
0.1093 Tw
T*
(activities are crucial for this function\054 and through this pathway) Tj
-0.00439 Tc
0.04939 Tw
T*
(XPD seems to play important roles in surviving mutagenic attacks) Tj
-0.005 Tc
0.02499 Tw
T*
(and in preventing premature aging\056) Tj
0.005 Tc
0.25529 Tw
0.947 -1.158 Td
(The cyclin\055dependent kinase \050Cdk\051\055activating kinase \050CAK\051) Tj
0.09219 Tw
-0.947 -1.158 Td
(complex consists of Cdk7\054 Mat1 and cyclin H\056 It is present as a) Tj
0.0043 Tc
0.0407 Tw
T*
(subcomplex of TFIIH or as free trimeric CAK\056 Although the free) Tj
0.005 Tc
0.1927 Tw
T*
(form activates the cell cycle Cdks\054 the TFIIH\055associated CAK) Tj
-0.005 Tc
0.01649 Tw
T*
(complex seems to primarily act in transcription by phosphorylating) Tj
-0.01151 Tc
0.0065 Tw
T*
[ (RNA) 55 ( polymerase II at its C\055terminal domain \050Rossignol et al\056\054 1997\073) ] TJ
0.005 Tc
0.064 Tw
T*
[ (Y) 100 (ankulov and Bentley) 65 (\054 1997\073 Larochelle et al\056\054 2006\051\056 Because it) ] TJ
0.09911 Tw
T*
(associates with CAK and core TFIIH \050cTFIIH\051\054 XPD can act as) Tj
-0.005 Tc
0.0462 Tw
T*
(bridge between the CAK complex and TFIIH and thereby regulate) Tj
0.005 Tc
0.0885 Tw
T*
[ (the dif) 18 (ferent activities of CAK \050Roy et al\056\054 1994\073 Drapkin et al\056\054) ] TJ
-0.005 Tc
0.0352 Tw
T*
[ (1996\073 Sandrock and Egly) 65 (\054 2001\073 Chen et al\056\054 2003\073 Li et al\056\054 2010\051\056) ] TJ
/TT5 1 Tf
0.0004 Tc
0 Tw
T*
[ (Dr) 37 (osophila) ] TJ
/TT4 1 Tf
0.0446 Tw
4.818 0 Td
(embryos lacking Xpd display a high frequency of cell) Tj
0.005 Tc
0.1958 Tw
-4.818 -1.158 Td
(cycle problems associated with severe chromosomal instability) Tj
-0.01469 Tc
0.0097 Tw
T*
(during mitosis\056 It is therefore conceivable that reduced ) Tj
/TT5 1 Tf
0 Tw
21.316 0 Td
(XPD) Tj
/TT4 1 Tf
2.145 0 Td
(function) Tj
0.0015 Tc
0.0435 Tw
-23.46 -1.158 Td
(during human mitosis causes also cell cycle problems that lead to) Tj
0.005 Tc
0.3484 Tw
T*
[ (chromosomal instability) 65 (\056 T) 70 (o better understand how the ) ] TJ
/TT5 1 Tf
0 Tw
24.736 0 Td
(XPD) Tj
/TT4 1 Tf
0.00391 Tc
0.04111 Tw
-24.736 -1.158 Td
[ (mutations af) 18 (fect the dif) 18 (ferent TFIIH complexes\054 it is important to) ] TJ
ET
1 1 1 scn
/GS1 gs
491.398 750.728 75.247 20.389 re
f
/Document /MC0 BDC
Q
Q
1 0 0 1 501.309 770.404 cm
/CS0 cs
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h
-2.988 4 m
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2.853 -0.01 m
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1 0 0 1 16.307 7.924 cm
0.13699 0.12199 0.125 scn
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f
1 0 0 1 2.134 -1.867 cm
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1.106 1.705 0.636 2.162 0 2.162 c
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h
0 2.536 m
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f
1 0 0 1 1.207 1.593 cm
0 0 m
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h
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1.098 1.242 1.38 0.877 1.38 0.428 c
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f
1 0 0 1 2.231 -0.391 cm
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0.424 1.027 l
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h
1.842 -1.202 m
1.426 -1.202 l
1.047 -0.366 l
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0.287 1.65 l
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f
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h
0 2.536 m
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h
0 4.711 m
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h
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1.56 9.266 l
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3.213 4.243 l
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f
1 0 0 1 8.096 -1.373 cm
0 0 -1.388 7.005 re
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f
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0 0 m
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0.951 2.324 0 1.342 0 0 c
h
6.068 0 m
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4.477 3.572 6.068 2.075 6.068 0 c
f
1 0 0 1 -523.632 -757.867 cm
530.495 754.295 1.388 10.639 re
f
1 0 0 1 534.099 757.867 cm
0 0 m
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0.951 2.324 0 1.342 0 0 c
h
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f
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h
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h
3.307 0.125 m
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3.307 1.202 l
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f
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f
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