0 9 Competent competent JJ 10 23 transcription transcription NN 24 34 initiation initiation NN 35 37 by by IN 38 41 RNA RNA NNP 42 52 polymerase polymerase NN 53 55 II ii CD 56 58 in in IN 59 68 cell-free cell-free JJ 69 77 extracts extract NNS 78 82 from from IN 83 92 xeroderma xeroderma NN 93 104 pigmentosum pigmentosum NN 105 111 groups group NNS 112 113 B B NNP 114 117 and and CC 118 119 D D NNP 120 122 in in IN 123 125 an an DT 126 135 optimized optimize VBN 136 139 RNA RNA NNP 140 153 transcription transcription NN 154 159 assay assay NN 159 160 . . . 162 165 The the DT 166 171 human human JJ 172 181 autosomal autosomal JJ 182 191 recessive recessive JJ 192 199 disease disease NN 199 200 , , , 201 210 xeroderma xeroderma NN 211 222 pigmentosum pigmentosum NN 223 224 ( ( ( 224 226 XP XP NNP 226 227 ) ) ) 227 228 , , , 229 232 can can MD 233 239 result result VB 240 244 from from IN 245 254 mutations mutation NNS 255 257 in in IN 258 261 any any DT 262 265 one one CD 266 268 of of IN 269 274 seven seven CD 275 280 genes gene NNS 280 281 , , , 282 292 designated designate VBN 293 296 XPA XPA NNP 297 304 through through IN 305 308 XPG XPG NNP 308 309 . . . 310 312 Of of IN 313 318 these these DT 318 319 , , , 320 323 the the DT 324 327 XPB XPB NNP 328 331 and and CC 332 335 XPD XPD NNP 336 341 genes gene NNS 342 348 encode encode VBP 349 357 proteins protein NNS 358 362 that that WDT 363 366 are be VBP 367 375 subunits subunit NNS 376 378 of of IN 379 380 a a DT 381 388 general general JJ 389 402 transcription transcription NN 403 409 factor factor NN 409 410 , , , 411 416 TFIIH TFIIH NNP 416 417 , , , 418 426 involved involve VBN 427 429 in in IN 430 434 both both CC 435 445 nucleotide nucleotide NN 446 454 excision excision NN 455 461 repair repair NN 462 463 ( ( ( 463 466 NER NER NNP 466 467 ) ) ) 468 471 and and CC 472 482 initiation initiation NN 483 485 of of IN 486 490 mRNA mrna NN 491 504 transcription transcription NN 505 507 by by IN 508 511 RNA RNA NNP 512 522 polymerase polymerase NN 523 525 II ii CD 525 526 . . . 527 529 In in IN 530 536 humans human NNS 536 537 , , , 538 546 mutation mutation NN 547 549 of of IN 550 553 the the DT 554 557 XPB XPB NNP 558 560 or or CC 561 564 XPD XPD NNP 565 569 gene gene NN 570 577 impairs impair VBZ 578 581 NER ner NN 581 582 , , , 583 592 resulting result VBG 593 595 in in IN 596 613 hyper-sensitivity hyper-sensitivity NN 614 616 to to TO 617 625 sunlight sunlight NN 626 629 and and CC 630 637 greatly greatly RB 638 647 increased increase VBN 648 652 skin skin NN 653 658 tumor tumor NN 659 668 formation formation NN 668 669 . . . 670 677 However however RB 677 678 , , , 679 681 no no DT 682 695 transcription transcription NN 696 706 deficiency deficiency NN 707 710 has have VBZ 711 715 been be VBN 716 728 demonstrated demonstrate VBN 729 731 in in IN 732 738 either either CC 739 743 XP-B XP-B NNP 744 746 or or CC 747 751 XP-D XP-D NNP 751 752 . . . 753 755 We we PRP 756 760 have have VBP 761 769 employed employ VBN 770 772 an an DT 773 782 optimized optimize VBN 783 792 cell-free cell-free JJ 793 796 RNA RNA NNP 797 810 transcription transcription NN 811 816 assay assay NN 817 819 to to TO 820 827 analyze analyze VB 828 841 transcription transcription NN 842 850 activity activity NN 851 853 of of IN 854 858 XP-B XP-B NNP 859 862 and and CC 863 867 XP-D XP-D NNP 867 868 . . . 869 877 Although although IN 878 881 the the DT 882 888 growth growth NN 889 893 rate rate NN 894 897 was be VBD 898 904 normal normal JJ 904 905 , , , 906 909 the the DT 910 914 XP-B XP-B NNP 915 918 and and CC 919 923 XP-D XP-D NNP 924 929 cells cell NNS 930 939 contained contain VBD 940 947 reduced reduce VBN 948 955 amounts amount NNS 956 958 of of IN 959 964 TFIIH TFIIH NNP 964 965 . . . 966 974 Extracts extract NNS 975 983 prepared prepare VBN 984 988 from from IN 989 993 XP-B XP-B NNP 994 997 and and CC 998 1002 XP-D XP-D NNP 1003 1017 lymphoblastoid lymphoblastoid JJ 1018 1023 cells cell NNS 1024 1033 exhibited exhibit VBD 1034 1041 similar similar JJ 1042 1055 transcription transcription NN 1056 1064 activity activity NN 1065 1069 from from IN 1070 1073 the the DT 1074 1084 adenovirus adenovirus NN 1085 1090 major major JJ 1091 1095 late late JJ 1096 1104 promoter promoter NN 1105 1109 when when WRB 1110 1118 compared compare VBN 1119 1121 to to TO 1122 1126 that that DT 1127 1129 in in IN 1130 1138 extracts extract NNS 1139 1143 from from IN 1144 1150 normal normal JJ 1151 1156 cells cell NNS 1156 1157 . . . 1158 1162 Thus thus RB 1162 1163 , , , 1164 1166 we we PRP 1167 1175 conclude conclude VBP 1176 1180 that that IN 1181 1184 the the DT 1185 1189 XP-B XP-B NNP 1190 1193 and and CC 1194 1198 XP-D XP-D NNP 1199 1213 lymphoblastoid lymphoblastoid JJ 1214 1219 cells cell NNS 1220 1222 do do VBP 1223 1226 not not RB 1227 1231 have have VB 1232 1240 impaired impair VBN 1241 1244 RNA RNA NNP 1245 1258 transcription transcription NN 1259 1267 activity activity NN 1267 1268 . . . 1269 1271 We we PRP 1272 1280 consider consider VBP 1281 1284 the the DT 1285 1293 possible possible JJ 1294 1306 consequences consequence NNS 1307 1309 of of IN 1310 1313 the the DT 1314 1321 reduced reduce VBN 1322 1330 cellular cellular JJ 1331 1338 content content NN 1339 1341 of of IN 1342 1347 TFIIH TFIIH NNP 1348 1351 for for IN 1352 1355 the the DT 1356 1364 clinical clinical JJ 1365 1373 symptoms symptom NNS 1374 1376 in in IN 1377 1381 XP-B XP-B NNP 1382 1384 or or CC 1385 1389 XP-D XP-D NNP 1390 1398 patients patient NNS 1398 1399 , , , 1400 1403 and and CC 1404 1411 discuss discuss VBP 1412 1413 a a DT 1414 1415 ‘ ` `` 1415 1426 conditional conditional JJ 1427 1436 phenotype phenotype NN 1436 1437 ’ ' '' 1438 1442 that that WDT 1443 1446 may may MD 1447 1454 involve involve VB 1455 1457 an an DT 1458 1468 impairment impairment NN 1469 1471 of of IN 1472 1480 cellular cellular JJ 1481 1489 function function NN 1490 1494 only only RB 1495 1500 under under IN 1501 1508 certain certain JJ 1509 1515 growth growth NN 1516 1526 conditions condition NNS 1526 1527 . . .