LOCUS       NM_007027               5761 bp    mRNA    linear   PRI 09-FEB-2025
DEFINITION  Homo sapiens DNA topoisomerase II binding protein 1 (TOPBP1),
            transcript variant 1, mRNA.
ACCESSION   NM_007027
VERSION     NM_007027.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 5761)
  AUTHORS   Egger,T., Morano,L., Blanchard,M.P., Basbous,J. and Constantinou,A.
  TITLE     Spatial organization and functions of Chk1 activation by TopBP1
            biomolecular condensates
  JOURNAL   Cell Rep 43 (4), 114064 (2024)
   PUBMED   38578830
  REMARK    GeneRIF: Spatial organization and functions of Chk1 activation by
            TopBP1 biomolecular condensates.
REFERENCE   2  (bases 1 to 5761)
  AUTHORS   Sun,X., Dong,M., Li,J., Sun,Y., Gao,Y., Wang,Y., Du,L., Liu,Y.,
            Ji,K., He,N., Wang,J., Zhang,M., Song,H., Xu,C. and Liu,Q.
  TITLE     NRF2 promotes radiation resistance by cooperating with TOPBP1 to
            activate the ATR-CHK1 signaling pathway
  JOURNAL   Theranostics 14 (2), 681-698 (2024)
   PUBMED   38169561
  REMARK    GeneRIF: NRF2 promotes radiation resistance by cooperating with
            TOPBP1 to activate the ATR-CHK1 signaling pathway.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 5761)
  AUTHORS   Prabhakar,A.T., James,C.D., Fontan,C.T., Otoa,R., Wang,X.,
            Bristol,M.L., Yeager,C., Hill,R.D., Dubey,A., Wu,S.-Y.,
            Chiang,C.-M. and Morgan,I.M.
  TITLE     Direct interaction with the BRD4 carboxyl-terminal motif (CTM) and
            TopBP1 is required for human papillomavirus 16 E2 association with
            mitotic chromatin and plasmid segregation function
  JOURNAL   J Virol 97 (10), e0078223 (2023)
   PUBMED   37712702
  REMARK    GeneRIF: Direct interaction with the BRD4 carboxyl-terminal motif
            (CTM) and TopBP1 is required for human papillomavirus 16 E2
            association with mitotic chromatin and plasmid segregation
            function.
REFERENCE   4  (bases 1 to 5761)
  AUTHORS   Gelot,C., Kovacs,M.T., Miron,S., Mylne,E., Haan,A.,
            Boeffard-Dosierre,L., Ghouil,R., Popova,T., Dingli,F., Loew,D.,
            Guirouilh-Barbat,J., Del Nery,E., Zinn-Justin,S. and Ceccaldi,R.
  TITLE     Poltheta; is phosphorylated by PLK1 to repair double-strand breaks
            in mitosis
  JOURNAL   Nature 621 (7978), 415-422 (2023)
   PUBMED   37674080
  REMARK    Erratum:[Nature. 2024 Feb;626(7999):E13. doi:
            10.1038/s41586-024-07025-8.. PMID: 38273133]
REFERENCE   5  (bases 1 to 5761)
  AUTHORS   Trivedi,P., Steele,C.D., Au,F.K.C., Alexandrov,L.B. and
            Cleveland,D.W.
  TITLE     Mitotic tethering enables inheritance of shattered micronuclear
            chromosomes
  JOURNAL   Nature 618 (7967), 1049-1056 (2023)
   PUBMED   37316668
REFERENCE   6  (bases 1 to 5761)
  AUTHORS   Honda,Y., Tojo,M., Matsuzaki,K., Anan,T., Matsumoto,M., Ando,M.,
            Saya,H. and Nakao,M.
  TITLE     Cooperation of HECT-domain ubiquitin ligase hHYD and DNA
            topoisomerase II-binding protein for DNA damage response
  JOURNAL   J Biol Chem 277 (5), 3599-3605 (2002)
   PUBMED   11714696
REFERENCE   7  (bases 1 to 5761)
  AUTHORS   Makiniemi,M., Hillukkala,T., Tuusa,J., Reini,K., Vaara,M.,
            Huang,D., Pospiech,H., Majuri,I., Westerling,T., Makela,T.P. and
            Syvaoja,J.E.
  TITLE     BRCT domain-containing protein TopBP1 functions in DNA replication
            and damage response
  JOURNAL   J Biol Chem 276 (32), 30399-30406 (2001)
   PUBMED   11395493
REFERENCE   8  (bases 1 to 5761)
  AUTHORS   Potter,T., Gohde,W., Wedemeyer,N. and Kohnlein,W.
  TITLE     Keratinocytes exposed to ultraviolet radiation reveal three
            down-regulated genes with potential function in differentiation and
            cell cycle control
  JOURNAL   Radiat Res 154 (2), 151-158 (2000)
   PUBMED   10931686
REFERENCE   9  (bases 1 to 5761)
  AUTHORS   Yamane,K. and Tsuruo,T.
  TITLE     Conserved BRCT regions of TopBP1 and of the tumor suppressor BRCA1
            bind strand breaks and termini of DNA
  JOURNAL   Oncogene 18 (37), 5194-5203 (1999)
   PUBMED   10498869
REFERENCE   10 (bases 1 to 5761)
  AUTHORS   Yamane,K., Kawabata,M. and Tsuruo,T.
  TITLE     A DNA-topoisomerase-II-binding protein with eight repeating regions
            similar to DNA-repair enzymes and to a cell-cycle regulator
  JOURNAL   Eur J Biochem 250 (3), 794-799 (1997)
   PUBMED   9461304
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC083905.20, BC032633.1,
            BC126209.1, BC151237.1 and AC016255.24.
            
            On May 17, 2019 this sequence version replaced NM_007027.3.
            
            Summary: This gene encodes a binding protein which interacts with
            the C-terminal region of topoisomerase II beta. This interaction
            suggests a supportive role for this protein in the catalytic
            reactions of topoisomerase II beta through transient breakages of
            DNA strands. [provided by RefSeq, Jul 2008].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC151237.1, D87448.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000260810.10/ ENSP00000260810.5
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-48                AC083905.20        97860-97907
            49-158              BC032633.1         12-121
            159-5306            BC126209.1         1-5148
            5307-5394           BC151237.1         5212-5299
            5395-5761           AC016255.24        51730-52096
FEATURES             Location/Qualifiers
     source          1..5761
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3q22.1"
     gene            1..5761
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /note="DNA topoisomerase II binding protein 1"
                     /db_xref="GeneID:11073"
                     /db_xref="HGNC:HGNC:17008"
                     /db_xref="MIM:607760"
     exon            1..173
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            174..264
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     CDS             181..4749
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /note="isoform 1 is encoded by transcript variant 1; DNA
                     topoisomerase 2-binding protein 1; DNA topoisomerase
                     II-beta-binding protein 1; topoisomerase (DNA) II binding
                     protein 1"
                     /codon_start=1
                     /product="DNA topoisomerase 2-binding protein 1 isoform 1"
                     /protein_id="NP_008958.2"
                     /db_xref="CCDS:CCDS46919.1"
                     /db_xref="GeneID:11073"
                     /db_xref="HGNC:HGNC:17008"
                     /db_xref="MIM:607760"
                     /translation="MSRNDKEPFFVKFLKSSDNSKCFFKALESIKEFQSEEYLQIITE
                     EEALKIKENDRSLYICDPFSGVVFDHLKKLGCRIVGPQVVIFCMHHQRCVPRAEHPVY
                     NMVMSDVTISCTSLEKEKREEVHKYVQMMGGRVYRDLNVSVTHLIAGEVGSKKYLVAA
                     NLKKPILLPSWIKTLWEKSQEKKITRYTDINMEDFKCPIFLGCIICVTGLCGLDRKEV
                     QQLTVKHGGQYMGQLKMNECTHLIVQEPKGQKYECAKRWNVHCVTTQWFFDSIEKGFC
                     QDESIYKTEPRPEAKTMPNSSTPTSQINTIDSRTLSDVSNISNINASCVSESICNSLN
                     SKLEPTLENLENLDVSAFQAPEDLLDGCRIYLCGFSGRKLDKLRRLINSGGGVRFNQL
                     NEDVTHVIVGDYDDELKQFWNKSAHRPHVVGAKWLLECFSKGYMLSEEPYIHANYQPV
                     EIPVSHKPESKAALLKKKNSSFSKKDFAPSEKHEQADEDLLSQYENGSSTVVEAKTSE
                     ARPFNDSTHAEPLNDSTHISLQEENQSSVSHCVPDVSTITEEGLFSQKSFLVLGFSNE
                     NESNIANIIKENAGKIMSLLSRTVADYAVVPLLGCEVEATVGEVVTNTWLVTCIDYQT
                     LFDPKSNPLFTPVPVMTGMTPLEDCVISFSQCAGAEKESLTFLANLLGASVQEYFVRK
                     SNAKKGMFASTHLILKERGGSKYEAAKKWNLPAVTIAWLLETARTGKRADESHFLIEN
                     STKEERSLETEITNGINLNSDTAEHPGTRLQTHRKTVVTPLDMNRFQSKAFRAVVSQH
                     ARQVAASPAVGQPLQKEPSLHLDTPSKFLSKDKLFKPSFDVKDALAALETPGRPSQQK
                     RKPSTPLSEVIVKNLQLALANSSRNAVALSASPQLKEAQSEKEEAPKPLHKVVVCVSK
                     KLSKKQSELNGIAASLGADYRWSFDETVTHFIYQGRPNDTNREYKSVKERGVHIVSEH
                     WLLDCAQECKHLPESLYPHTYNPKMSLDISAVQDGRLCNSRLLSAVSSTKDDEPDPLI
                     LEENDVDNMATNNKESAPSNGSGKNDSKGVLTQTLEMRENFQKQLQEIMSATSIVKPQ
                     GQRTSLSRSGCNSASSTPDSTRSARSGRSRVLEALRQSRQTVPDVNTEPSQNEQIIWD
                     DPTAREERARLASNLQWPSCPTQYSELQVDIQNLEDSPFQKPLHDSEIAKQAVCDPGN
                     IRVTEAPKHPISEELETPIKDSHLIPTPQAPSIAFPLANPPVAPHPREKIITIEETHE
                     ELKKQYIFQLSSLNPQERIDYCHLIEKLGGLVIEKQCFDPTCTHIVVGHPLRNEKYLA
                     SVAAGKWVLHRSYLEACRTAGHFVQEEDYEWGSSSILDVLTGINVQQRRLALAAMRWR
                     KKIQQRQESGIVEGAFSGWKVILHVDQSREAGFKRLLQSGGAKVLPGHSVPLFKEATH
                     LFSDLNKLKPDDSGVNIAEAAAQNVYCLRTEYIADYLMQESPPHVENYCLPEAISFIQ
                     NNKELGTGLSQKRKAPTEKNKIKRPRVH"
     exon            265..399
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            400..543
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            544..725
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            726..922
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            923..1102
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1103..1269
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1270..1433
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1434..1684
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1685..2028
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2029..2201
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2202..2413
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2414..2700
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2701..2874
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2875..2984
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2985..3108
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            3109..3255
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            3256..3358
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            3359..3551
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            3552..3772
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            3773..3939
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            3940..4051
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            4052..4215
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            4216..4353
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            4354..4443
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            4444..4605
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     exon            4606..5761
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4938..4943
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /note="hexamer: AATAAA"
     polyA_site      4967
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
     regulatory      5330..5335
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /note="hexamer: AATAAA"
     polyA_site      5349
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /note="major polyA site"
     regulatory      5374..5379
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
                     /note="hexamer: GATAAA"
     polyA_site      5394
                     /gene="TOPBP1"
                     /gene_synonym="Dpb11; TOP2BP1"
ORIGIN      
        1 agtcggttcc cgttctgggc aatttccggg ttctccagcg tttgctttgg ggtaggggcg
       61 gcgccgagtc gggggagggg gctgtgcgcc gggctggcgc ccgaccccag ccaccgccct
      121 gcggccagcg cgtcccccga ctcgccgccc ggagaccccg aggctccaac gagttcagaa
      181 atgtccagaa atgacaaaga accgtttttt gtgaagtttt taaagtcttc agacaattcc
      241 aaatgttttt ttaaagctct cgagtccata aaagaattcc aatcagaaga atatcttcag
      301 attattacag aagaagaggc attgaagata aaggagaatg atagatcact ttatatctgt
      361 gaccctttta gtggcgttgt ctttgatcac ctcaaaaagc ttggctgcag aattgttggt
      421 cctcaagtag tcatattttg tatgcaccac cagcgatgtg tcccaagagc cgaacatcca
      481 gtttataata tggttatgtc tgatgtaacc atatcttgta caagtctgga aaaagaaaaa
      541 agggaagaag ttcataaata tgtacaaatg atgggcggac gagtatacag agaccttaat
      601 gtatcagtaa ctcaccttat tgcaggagaa gttggtagca aaaaatattt agttgctgca
      661 aacctgaaga aacctatttt gcttccctct tggataaaaa cactttggga gaagtcacaa
      721 gagaaaaaaa taactagata tactgatata aacatggaag atttcaagtg tcctattttt
      781 cttggttgca taatctgtgt gactggctta tgtggcttag acaggaaaga agttcagcaa
      841 ctcacagtta agcatggagg tcaatacatg ggacaattga aaatgaatga atgtacacac
      901 ctcattgtgc aagaaccaaa aggtcagaag tatgagtgtg ccaagagatg gaatgtacac
      961 tgtgtgacca cacagtggtt ttttgacagt attgagaaag gtttttgtca ggatgaatcc
     1021 atatacaaga cagaacctag accagaagca aagactatgc ccaattcttc aactcctacc
     1081 agccagatca acacaattga tagtcgtact ctttcagatg tcagcaatat ttccaacata
     1141 aatgcaagtt gcgtaagtga atcaatatgt aattcactta acagcaaact ggagcctaca
     1201 cttgaaaatc tagaaaatct ggatgtcagt gcatttcaag cacctgaaga tttattagat
     1261 ggttgtcgga tatatctttg cggttttagt ggcagaaagc tagataaact gagaagactt
     1321 attaacagtg gaggtggagt tcgttttaac cagctaaatg aagatgtaac tcatgttatt
     1381 gtgggagatt atgatgatga attgaagcag ttttggaata aatcagccca caggcctcat
     1441 gtagtgggag caaagtggtt gctagagtgt ttcagtaaag gttatatgct ttctgaagaa
     1501 ccatatatcc atgctaatta ccagccagtg gaaattccag tttcacataa gcctgaaagt
     1561 aaagcagctc ttttaaaaaa gaagaacagc agcttctcta agaaagactt tgctcctagt
     1621 gaaaagcatg agcaagctga tgaagatctg ctctctcaat atgaaaatgg tagctccaca
     1681 gtagttgagg ctaagacgtc tgaagccagg ccctttaatg attctactca tgctgagccc
     1741 ttgaatgatt ctactcacat ttctttgcaa gaagaaaacc agtcttctgt cagtcattgt
     1801 gtccctgatg tttctacaat tactgaagaa ggcttattta gccaaaagag tttccttgtt
     1861 ttgggtttta gtaatgaaaa tgaatctaac atcgcaaaca tcataaaaga aaatgctggg
     1921 aaaatcatgt cccttctgag cagaactgtt gcggattatg ctgtggttcc tctgctgggg
     1981 tgtgaagtgg aagccactgt gggagaagtt gttacaaata catggctggt tacttgcata
     2041 gactatcaga ctttgtttga tccaaagtcg aatcctctct tcacaccagt tccagtaatg
     2101 acaggaatga ctcctttaga ggattgtgtt atttcattta gccagtgtgc tggagcagaa
     2161 aaagagtctt taacattcct agcaaacctc cttggagcaa gtgttcaaga atactttgtt
     2221 cgcaaatcca atgcaaagaa aggcatgttt gccagtactc atcttatact gaaagaacgt
     2281 ggtggctcta aatatgaagc tgcaaagaag tggaatttac ctgccgttac tatagcttgg
     2341 ctgttggaga ctgctagaac gggaaagaga gcagacgaaa gccattttct gattgaaaat
     2401 tcaactaaag aagaacgaag tttggaaaca gaaataacaa atggaatcaa tctaaattca
     2461 gatactgcag agcatcctgg cacacgcctg caaactcaca gaaaaaccgt cgttacacct
     2521 ttagatatga accgctttca gagtaaagct ttccgtgctg tggtctcaca acatgccaga
     2581 caggtcgcag cctccccagc agtaggacaa ccacttcaga aggagccctc gttacacctg
     2641 gatacaccat caaaattcct gtccaaggac aaactcttca agccttcctt tgatgtgaag
     2701 gatgcacttg cagccttgga aactccagga cgtcccagcc aacagaaaag gaaaccgagt
     2761 acgccactct cagaagttat tgtcaaaaac ttgcaacttg ctttggcaaa tagctctcga
     2821 aatgctgtcg ctctttctgc cagccctcaa ctgaaagagg cccagtcaga gaaggaagaa
     2881 gccccaaagc cacttcacaa agtagtggta tgtgttagta aaaaactcag taagaagcag
     2941 agtgaactaa atgggatcgc agcctctcta ggagcagatt acaggtggag ttttgatgaa
     3001 acagtgactc atttcatcta tcaagggcgg ccaaatgaca ctaatcggga gtataaatct
     3061 gtaaaagaaa gaggagtaca cattgtttcc gagcactggc ttttagattg tgcccaagag
     3121 tgtaaacatc ttcctgaatc tctttatcca catacttata atcccaaaat gagcttggat
     3181 atcagcgcag tgcaagatgg ccggctctgt aatagtcgac tactctcagc tgtgtcttca
     3241 acaaaggatg atgagccaga tcctttgatt ttagaagaaa atgatgtaga caatatggcc
     3301 accaataata aagagtcagc accatcaaat ggaagtggaa agaatgactc taaaggagtt
     3361 ctgacacaga ccttagagat gagagagaac tttcagaagc agttacagga gataatgtct
     3421 gcaacatcaa tagtgaaacc ccaagggcag aggacttccc tttcaagaag tggttgtaac
     3481 agcgcatctt caacccctga cagcactcgc tctgctcgca gtggacgaag tagagtccta
     3541 gaggcactga ggcagtctcg tcagacagta cctgatgtca acacagagcc ttcccaaaat
     3601 gaacagatca tttgggatga ccctacagca agggaggaga gagcaaggct tgccagcaat
     3661 ttgcagtggc ctagttgtcc cacacaatac tctgagcttc aggttgacat tcaaaacttg
     3721 gaggattctc cttttcaaaa gcctttacat gattcagaaa ttgctaaaca ggctgtctgt
     3781 gatcctggaa acatacgtgt gactgaagct cccaaacacc caatctctga agaactggaa
     3841 actcccataa aagacagcca cctgatccct acgcctcaag cccccagtat tgcctttcca
     3901 ctcgccaacc cccctgtggc tccgcaccct agagaaaaga ttataacgat agaggagact
     3961 catgaagaat taaaaaaaca gtacatattt cagttatcat ctctgaatcc tcaagaacgt
     4021 attgactatt gtcatctgat tgagaaacta ggtggattgg tgatagaaaa gcagtgcttt
     4081 gatcccacct gtacacacat tgttgtggga catccacttc gaaacgagaa gtatttagcc
     4141 tcagtggcag ctgggaagtg ggtgcttcat cgctcctacc ttgaagcctg caggactgct
     4201 ggacacttcg tgcaggaaga agactatgaa tggggaagta gttccatact tgatgttctg
     4261 actggaatca atgtacagca acgaagacta gcacttgcag caatgagatg gagaaaaaaa
     4321 atccagcaaa gacaagaatc tggcattgtt gagggagcat ttagtgggtg gaaggttatt
     4381 ttacatgtgg atcagtctcg agaagcaggc ttcaaacgcc ttcttcagtc aggaggagca
     4441 aaggtgctac ctggtcattc tgtaccttta tttaaagagg ccacacatct tttttctgac
     4501 ttgaataaac tgaaaccaga tgactcagga gttaatatag cagaagctgc tgcccagaac
     4561 gtgtactgct tgagaacaga atacattgct gattatctca tgcaggaatc acctcctcat
     4621 gtagaaaatt actgtctacc agaagctatt tcatttattc agaataataa ggaacttggg
     4681 actggattat cacaaaagag gaaagctcct acagaaaaaa ataaaatcaa acgacctaga
     4741 gtacactaat cgcatctacc ctttagttac caaacattaa atgtttttaa aaattgaaag
     4801 cctgaatgtg actgtgatag atttgggtag taatttaaag atgagtacct gaagaattct
     4861 gcttcagagt ataatgatga cccttcttga gttttgaaca cctgaaattg taatcactga
     4921 aatattaact gtttcttaat aaaaagttac ctgaaataac aacaaaatac aactcctcag
     4981 ctagcttgct gttaaaccac attgaagtct gttaaaagat atttattttt cttgtaaata
     5041 tctgaagctg tagcttagtg gaaattttag caaggtaatg gattttgctt taaaatgtct
     5101 gccttacaaa ttcataacaa caagatttgt cagtcagcat ttattcatgt tttccctgat
     5161 ttttatcttc tcaccatttt acctctttta acaggagcct gagcacaagg tttaatgagg
     5221 aagctggggc tataaatatg tgtgtatata tgtatatgta tgtttgtaca aatctccatg
     5281 atgtttgcca agtttgaatg cgcaaaactt ggaaaatgtg acaataaaga ataaaagtag
     5341 taactcaaat tagtattaag atgtgtttac atagataaat tttttaaaag agcaccctgg
     5401 catctgttct tctgttgaag caacaaaaca tttatgtaac gtaaaaaatg aattgcaggg
     5461 gcctgggtgc ggtggctcgt gcctgtaatc ccagcacttt gggaggctga ggcaggcgga
     5521 tcgtctgagg tcgggagttt gagaccagcc tgaccaacat ggagaaacct catctgtact
     5581 aaaaatacaa aaaattagcc cagtgtggtg gcacatgcct gtaatcccag ctactcagga
     5641 ggctgaggca ggagaatcgc ttgaacccgg gaggcggagg ttgcggtgag ctgagatcgc
     5701 gccattgcac tccagcctgg gcaacaagag cgaaactcca tctcaaaaaa aaaaaaaaaa
     5761 a
//
