outline of the dna ber pathways in mammals
DESCRIPTION
3D. Outline of the DNA BER pathways in mammals. Nucleotides excision repair. Sequences and organization of rat PCNA promoter. Rat PCNA Promoters. -693 -240 -70 +125. CAT. d693. d240. d70. - 70 +125. - PowerPoint PPT PresentationTRANSCRIPT
Title:
The Regulation of Proliferating Cell Nuclear Antigen Gene
Expression in UV Inducibility and Serum Responsiveness
增生細胞核抗原在紫外線與血清反應的調節
學號姓名 張學偉 Hsueh-Wei Chang
指導教授 劉銀樟 Yin-Chang Liu
3D
PCNA-interacting proteins: binding, recognition and function*
Binding sites onPCNA
Protein /Complex1
Centerloop
(Asp41-His44)
Inter-domain
connectingloop
(Leu121-Glu132)
C-endTail
(Lys254-Glu256)
DNArecognition site
Function of interactionwith PCNA
EnzymesRF-C + - + Primer terminus Loading/unloading of PCNA to DNA
by ATP binding/hydrolysis
DNA pol + + -DNA pol ND - +
Single-strand-duplexjunction
Processive DNA synthesis
Fen-1 + + + Flap structure Stimulates Fen-1 activity
DNA ligase I Nicks in DNA Okazaki-fragment maturation
DNA-MTase + + + CpG dinucleotide Brings DNA-MTase to newlyreplicated DNA
XP-G Single-strand-duplexjunction
MLH1MSH2
Base mismatch,insertions/deletions
Mismatch repair
UDG2 Uracil in DNA Base-excision repair
p150 of CAF1 Essential for the replication coupledchromatin assembly
WRN Copurify with PCNA and topo I
RNA pol Required for viral late genetranscription (baculovirus)
Regulatoryproteinsp21WAF1/Cip1 + + + Inhibits DNA synthesis
Gadd45 ND ND +Cyclin D Inhibits DNA synthesis
p57 Inhibits DNA synthesis
MyD118 Stimulates DNA synthesis ?
CRAMPED(CRM)
Product of a Drosophia melano-gastergene that was shown to interactgenetically with PCNA
Structures Role of PCNA in structure
Chromatin Assembly of chromatin ?
ReplisomeRepairsome
Scaffold for polymerases and otherenzymes
1Abbreviation: RF-C, Replication factor C; DNA pol, DNA polymerase; Fen-1, Flapendonuclease 1; DNA-MTase, DNA (cytosine-5) methyltransferase; XP-G, Xerodermapigmentosum G; UDG2, Uracil-DNA glycosylase 2; CAF-1, histone chaperone chromatinassembly factor 1; WRN, Werner syndrom gene product; gadd45, growth arrest and DNA damage;MyD118, Myeloid-differentiation primary-response. * [Jonsson, 1997 #7; Kelman, 1997 #8;Kelman, 1998 #3; Tsurimoto, 1999 #4; Warbrick, 1998 #6; Lebel, 1999 #9]
Outline of the DNA BER pathways in mammals
Nucleotides excision repair
MatInspector Result matrix matrix core matrix sequence name position(str) simil. simil.----------------------------------------------------------------------- Inspecting sequence rat PCNA promoter [-693 to +130]
E2F -373 (+) 0.857 0.854 TTTTgcgg E2F -359 (+) 0.857 0.867 TTTTacgc CEBPB_01 -324 (+) 0.873 0.856 gtttgaaGGAActa STAT_01 -322 (-) 1.000 0.873 TTCCttcaa IK2_01 -309 (-) 1.000 0.884 aagaGGGAgact USF_Q6 -279 (-) 0.864 0.874 gcCACTtgca NKX25_01 -278 (+) 1.000 0.946 gcAAGTg USF_C -278 (-) 0.836 0.919 cCACTTgc BARBIE_01 -275 (-) 1.000 0.856 aatgAAAGccacttg ELK1_02 -275 (-) 1.000 0.929 cgccacGGAAatga ELK1_02 -248 (-) 1.000 0.870 tccttaGGAAgttt OCT1_Q6 -236 (+) 0.800 0.860 gaacatggAAACcac CREL_01 -230 (-) 1.000 0.860 tgtggtTTCC PADS_C -229 (-) 1.000 0.950 tGTGGTttc IK2_01 -226 (-) 1.000 0.871 tggaGGGAgctt CP2_01 -224 (+) 1.000 0.871 gctccctCCAA E2_01 -207 (+) 1.000 0.871 ccaacaccggCGGTga CMYB_01 -206 (-) 1.000 0.853 ccggtGTTG
CREB -198 (+) 1.000 0.939 gcggTGACgaca ATF -197 (+) 1.000 0.956 cggTGACgacagcc AP1 -196 (+) 1.000 0.897 ggTGACgacag CREBP1 -196 (+) 1.000 0.877 ggTGACgacagc NMYC_01 -177 (+) 1.000 0.883 aacccCGTGatg IK2_01 -160 (-) 1.000 0.912 gcgtGGGAggcg NGFIC_01 -158 (-) 1.000 0.917 gaGCGTgggagg EGR3_01 -158 (-) 1.000 0.889 gaGCGTgggagg XBP1_01 -145 (-) 1.000 0.887 gaggcgACGTgtgcgta ARNT_01 -144 (-) 1.000 0.877 gaggcgaCGTGtgcgt
GC -123 (+) 1.000 0.884 acgcGGCGgggcgg SP1 -123 (+) 1.000 0.882 acgcGGCGgggcg AP2 -122 (-) 0.976 0.880 cgCCCCgccgcg GC -118 (+) 1.000 0.926 gcggGGCGggcctt SP1 -118 (+) 1.000 0.939 gcggGGCGggcct CEBP -112 (-) 0.992 0.871 tggtttgaGCAAGgcccg PADS_C -101 (-) 1.000 0.893 cGTGGTttg GFI1_01 -95 (-) 1.000 0.870 ccAATCgtatccgt NFY_Q6 -87 (-) 1.000 0.956 gaaCCAAtcgt CP2_01 -85 (-) 1.000 0.856 tctagaaCCAA
GC -69 (+) 0.872 0.875 ggtgGGTGggtcag SP1 -69 (+) 0.819 0.859 ggtgGGTGggtca AP1 -65 (-) 1.000 0.913 gcTGACccacc AP1 -64 (+) 0.848 0.851 gTGGGTCAg NFE2 -64 (-) 1.000 0.856 cgCTGAcccac AP4 -60 (+) 1.000 0.874 gtCAGCgctg CREB -54 (+) 1.000 0.887 gctgTGACgcca ATF -53 (+) 1.000 0.914 ctgTGACgccacaa AP1 -52 (+) 1.000 0.858 tgTGACgccac CREBP1 -52 (+) 1.000 0.884 tgTGACgccaca CMYB_01 -42 (-) 1.000 0.870 gcgagGTTG ELK1_02 -17 (+) 1.000 0.857 cgcctaGGAAgccg IK2_01 -16 (+) 0.826 0.858 gcctAGGAagcc
Quandt, K. Frech, K. Karas, H. Wingender, E. and Werner, T.MatInd and MatInspector - New fast and versatile tools for detection of consensus matches in nucleotide sequence dataNucleic Acids Research 23, 4878-4884 (1995)
Sequences and organization of rat PCNA promoter
Localization of UV inducibility in rat PCNA promoter
Promoter region Relative CAT activity U.V. - +
Foldactivation(+/-)
-693 +125 241.0± 24.2 477.0± 22.7 ~2.0
-240 +119 183.0± 30.2 426.3± 25.3 ~2.3
-70 +125 56.0± 21.9 114.7± 9.0 ~2.1
none 1.0 1.0 1.0
CAT
-693 -240 -70 +125
Rat PCNA Promoters
AP-1 ATF/CRE
TGGGTCAGCGCTGTGACGCCA
-70 +125
(-64/-58) (-51/-44)
Fold
act
ivat
ion
0
2
4
6
8
10
12
wild type mAP1 mATF mAP1 mATFwild type
Fold
act
ivat
ion
0
1
2
3
4
5UV Serum
d693d240
d70
UV
PCNA
Activation of p53-mediated gene expression in response to DNA damage
Metabolic pathways of reactive oxygen radicals
otherDNA-PK
UV
PCNA
?EMSA
promotermRNAprotrein
ATF-1
chapter 4
chapter 2
?
chapter 3
chapter 2
Outline of the thesis
chapter 2
HPVE6