DNA repl in eukaroyte
分子生物学chapter8
The first issue concerns the origin of replication.
Where along the chromosome is DNA replication initiated? Is there only a single origin, or does DNA synthesis begin at more than one point? Is a point of origin random or is it located at a specific region along the chromosome? Second ,once replication begins, does it proceed in a single direction or in both directions away from the origin? In other words, is replication unidirectional or bidirectional?
Polymerase I : three Active Sites on Its Single Polypeptide Chain
5' →3' polymerase activity: nucleotides
polymerization ,1000nt/min。 3'-5 ' exonuclease activity :remove incorrect (mismatched) bases.
• DNA polymerase II • DNA polymerase III
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E. coli DNA polymerase I
Purification and characterization by Arthur Kornberg
lecture2
One τ-subunit also contacts the DnaB helicase at the fork. This interaction strongly increases normally slow unwinding activity of the helicase.
Thus, there is a physical and functional link between the two major replication machines at the fork – the two core polymerases and the primosome complex of DnaB and primase.
Termination of DNA Replication
Removal of RNA primers DNA polymerase recognizes that it is not DNA-DNA duplex and:
removes the RNA primer, one ribonucleotide at a time (exonuclease activity) inserts a deoxyribonucleotide, complementary to the base of the template strand. repeats the process until all of the RNA is removed and replaced with DNA double strand. on the lagging strand, at the beginning of Okazaki fragments. on the leading strand at the replication origin.
DNA复制(DNA Replication)英文版
***大学
Elongation of DNA Replication
After RNA primer is synthetized later, the elongation of DNA
begins. The leading chain is continuously synthetized, and the lagging chain is discontinuously synthetized.In the replication fork, DNA helicase moves from 5' to 3' on the DNA template . DNA primase periodically bonds with helicase, and synthetizes new primer in the lagging chain template . Afteran Okazaki fragment is completely synthetized,the core which is responsible for the Okazaki fragment, slides from the sliding clamp and DNA.
***大学
Materials
●Template:One of the strand of dsDNA;
● dNTPs:4 kinbs of deoxynucleotide triphosphates, that's,ATP,GTP,CTP,TTP;
● Primer:usually RNA; ● Proteins and enzyme:such as DNA polymerase,DNA helicase,Singlestrand DNA binding protein （SSB）,DNA topoisomerase,DNA ligase,Telomerase (special in euka-ryotes);
3+DNA的复制
The replication of DNA
生命的遗传实际上是染色体DNA自我复制的结果
中心法则 DNA
遗传 物质 基 因 表 达Fra bibliotekRNA
翻 译
自 我 复 Protein 制 子 生理功能 代
运 输
表 型
解决的问题
DNA由一个拷贝变成两个拷贝 复制的准确性
DNA的半保留复制 （semiconservative replication）
T7 DNA pol
Thumb
Fingers
Palm
DNA 聚合酶的手掌结构域 (palm domain)
催化位点： dNTPs 的添加和去除
结合了两个二价金属离子，改变活性 位点周围的化学环境 (how?)
DNA 聚合酶的手指结构域 (finger domain) 结合进入的dNTP, 并将正确配对的 dNTP围住，为催化作准备 将模板DNA链弯曲，只暴露出一个碱 基和进入的dNTP 配对
复制起点(Origins of replication), 在复制起点处解开DNA双螺旋， 复制从这里开始
Initiation of DNA replication
复制起始的复制子模型
Proposed by Jacob and Brenner in 1963 All the DNA replicated from a particular origin is a replicon (复 制子) Two components, replicator ( 复 制基因) and initiator(起始因子), control the initiation of replication
第五章 DNA复制
SSB
DnaA
13bp repeats
涉及转录激活
一分子的 DNA pol III. 协同合成前导链和后随链
The βsubunit of DNA polymerase III consists of a head to tail dimer that forms a ring completely surrounding a DNA duplex.
真核生物（Eukaryote） : 多复制起点 即－－一个genome中有多个复制单位
2、复制方向（复制过程的顺序性） （1） 单双向复制取决于起点处有一个还是两个复制叉
单向复制
双向复制
（2） 复制的多模式
单起点、单方向 （原核）
多起点、单方向 （真核）
单起点、双方向（原核）
多起点、双方向（真核）
长的发 夹结构
4、 线性DNA的末端复制的问题
（1） 线状 DNA的复制5’末端短缩的解决模式
a、 从开始就采取环化的形式 －－－λ噬菌体 b、 象T7噬菌体一样采取连环分子的形式
利用自身线性DNA末端的重复序列－－ 通过末端互补形成连环分子 c、 最直接的办法－－－引入蛋白质直接从末端起始复制 如－－－腺病毒－2、phageΦ29、脊髓灰质炎病毒 d、 痘病病毒的末端由发夹结构连接 复制完成后错切连接
复制速度较慢,大 约 500~5000bp/min c、复制终止通过复制 叉的相遇而终止
d、真核生物复制起点
酵母DNA的复制起点 ♪ 酵母复制起点的鉴定方法 ♪ 酵母的复制起点称为:自主复制顺序 (autonomously replicating sequence,ARS) ♪ 酵母ARS已鉴定四个亚功能域:
第七讲-第十讲复制
• 1. 5‘→3’聚合功能 • 2. 3‘→5’外切活性 • 3. 5‘→3’外切活性
(1)切口平移（nick translation）； (2)链的置换； (3)模板转换（template-switching） • 4. 内切酶活性
5'
3'
3'
5'
GTAAGTCG
·····
C TCAGC
5'
2.DNA聚合酶的结构和功能
DNA聚合酶有6个结合位点： • (1) 模板结合位点； • (2) 引物结合位点； • (3) 引物3‘－OH结合位点； • (4) 底物dNTP结合位点； • (5) 5‘→3’外切酶结合位点； • (6) 3'→5'校正位点。
聚合
3'－5'外切 5'－3'外切 5'
一、Meselson-Stahl实验 二、Taylar实验 三、姐妹染色单体差别染色方法（sister-
chromatid differential staining）5溴脱氧尿嘧 啶（5-Bromodeoxy uridine，简称BUdR） 斑色染色体（Harlequin chromosome） 四、Cairns复制模型—θ型复制
叫全保留复制(conservative replication)
和分散模型（dispersive model）的复制
方式也是可能的。
第一节 半保留复制的验证
• 半 保 留 模 型 （ semioconservetive model）
• 全 保 留 复 制 模 型 (conservetive model)
核心酶 (165K) 合成 DNA
α：130 K(polC 即 dna E)— DNA 合成 ε：25K(dnaθ) —3'－5'外切酶活性,校对 θ ：10K—使核心酶相互连接。
dna replication
所有DNA的复制都是从固定起始点开始的，而目前已知的DNA聚合酶都只能延长已存在的DNA链，而不能从头合成DNA链，那么一个新DNA的复制是怎样开始的呢？研究发现，DNA复制时，往往先由RNA聚合酶在DNA模板上合成一段RNA引物，再由DNA聚合酶从RNA引物3′端开始合成新的DNA链。对于前导链来说，这一引发过程比较简单，只要有一段RNA引物，DNA聚合酶就能以此为起点一直合成下去。但对于滞后链来说，引发过程就十分复杂，需要多种蛋白质和酶的协同作用，还牵涉到冈崎片段的形成和连接。
（1）参与DNA复制的物质
DNA的复制是一个复杂的过程，需要DNA模板、合成原料──三磷酸核苷酸（dATP、dGTP、dCTP、dTTP）、酶和蛋白质等多种物质的参与。
解旋酶（helicase） DNA复制涉及的第一个问题就是DNA两条链要在复制叉位置解开。DNA双螺旋并不会自动解旋，细胞中有一类特殊的蛋白质可以促使DNA在复制叉处打开，这就是解旋酶。解旋酶可以和单链DNA以及ATP结合，利用ATP分解生成ADP时产生的能量沿DNA链向前运动促使DNA双链打开。
随着引发体合成RNA引物，DNA聚合酶Ⅲ全酶开始不断将引物延伸，合成DNA。DNA聚合酶Ⅲ全酶是一个多亚基复合二聚体，一个单体用于前导链的合成，另一个用于滞后链的合成，因此它可以在同一时间分别复制DNA前导链和滞后链。虽然DNA前导链和滞后链复制的方向不同，但如果滞后链模板环绕DNA聚合酶Ⅲ全酶，并通过DNA聚合酶Ⅲ，然后再折向未解链的双链DNA的方向上，则滞后链的合成可以和前导链合成在同一方向上进行。
滞后链的引发过程通常由引发体（primosome）来完成。引发体由6种蛋白质共同组成，只有当引发前体与引物酶（primase）组装成引发体后才能发挥其功效。引发体可以在滞后链分叉的方向上移动，并在模板上断断续续地引发生成滞后链的引物RNA。由于引发体在滞后链模板上的移动方向与其合成引物的方向相反，所以在滞后链上所合成的RNA引物非常短，长度一般只有3～5个核苷酸。
DNA Replication
耿红卫PH.D.cauglacier@Mol ecular BiologyThe Replication of DNADNA的复制1General features on DNA replication DNA复制的一般特点2DNA合成化学3DNA复制的酶学4DNA聚合酶5The mechanism of DNA replicationDNA 的复制过程1 General features on DNA replication1.1复制的忠实性和速度1.2半保留复制和半不连续复制DNA 复制的忠实性人类有30亿对碱基若每复制100万个碱基发生一次错误则每次有丝分裂产生3000个错误细胞中的复制错误率是每10亿个拷贝发生一次错误DNA 复制的速度大肠杆菌约有470万对碱基若每分钟复制1000个，染色体复制完毕需3天大肠杆菌能够每20分钟繁殖一代大肠杆菌的复制速度是每秒钟1000个碱基半保留复制产生两个子代DNAs ，每个分子都含有一个亲代链和一个新合成的链全保留复制分散复制半保留复制半不连续复制：一条链是连续合成的(前导链)，另一条链不是连续合成的(后随链)，是由多个片段连接而成，两条链的合成方向都是5’-3’Overview of DNA synthesis2 DNA 的合成化学2.1合成DNA 需要脱氧核苷三磷酸和引物2.2DNA 是通过延长引物的3’端合成的2.3DNA 合成酶仅有一个活性位点2.4DNA 聚合酶像一只右手握住引物和模板2.5核酸外切酶校对新合成的DNA2.1 合成DNA需要脱氧核苷三磷酸和引物DNA 合成需要两种关键底物1dGTP, dCTP, dATP, dTTP 四种脱氧核苷三磷酸2模板:引物的结合体Substrates required for DNA synthesisdsDNA: double strand DNA ssDNA: single strand DNA2.2 DNA是通过延长引物的3’端合成的DNA和RNA合成的特点新链是通过在引物的3’端延长的方式合成的DNA不能从头合成Priming in DNA synthesis2.3 DNA聚合酶仅有一个活性位点DNA polymerase (DNA聚合酶)DNA聚合酶仅有一个活性位点，催化四种脱氧核苷三磷酸的延长反应正确的碱基配对对于酶的催化是必须的脱氧核苷酸的加入对于酶的催化是必须的Correctly paired bases are required for DNA polymerasecatalyzed nucleotide additionSteric structure prevents catalysis using rNTPs by DNA polymeraseThe three-dimensional structure of DNA polymerase resemble a right handDNA聚合酶的三个主要功能区域手掌①由β折叠片构成②是主要的催化位点③监视碱基配对的正确性手指①也是重要的催化位点，与即将加入的dNTP结合②一旦形成正确的碱基配对，手指区域就将dNTP裹住大拇指①与新合成的DNA接触，保证引物和活性位点处于正确的位置②将酶和底物紧紧结合在一起DNA polymerase "grips" the template and the incomingnucleotide when a correct bade pair is madeThe path of the template DNA through the DNA polymerase 2.5 核酸外切酶校对新合成的DNA细胞中DNA复制的精确度很高细胞中大约每1010个碱基对发生一次错配DNA聚合酶平均每105个核苷酸接纳一个错误的核苷酸外切酶将错误率降低至每107发生一次错误外切酶类似“Backspace”按键，仅仅删除刚刚发生的错误当聚合酶检测到碱基发生错配手掌对错配DNA的结合力下降DNA从活性位点滑向外切酶位点错配碱基被删除DNA开始重新合成Proofreading exonucleases removes bases from the3' end of mismatched DNADNA polymerase (P) and exonuclease (E) activities of theKlenow fragment of DNA polymerase Ⅰin E. coli.3 DNA 复制的酶学3.1DNA 的两条链在复制叉上同时合成3.2DNA 新链的合成需要一个RNA 引物3.3RNA 引物必须被除去3.4DNA 解旋酶在复制叉前方解开DNA 双链3.5单链结合蛋白在DNA 复制前能稳定单链结构3.6拓扑异构酶除去DNA 解链形成的超螺旋3.1 DNA的两条链在复制叉上同时合成The replication fork前导链后随链Replication fork复制叉Region where the enzymes replicating a DNA molecule are bound tountwisted, single stranded DNA复制DNA 的酶与解旋的单链DNA 结合的区域DNA synthesis takes place simultaneously but in opposite direction on the two DNA template strands 3.2 DNA新链的合成需要一个RNA引物DNA的合成需要一个游离的3’羟基1DNA聚合酶不能从头合成DNA，只能以添加脱氧核苷酸的方式延长2引物酶(primase)是RNA聚合酶，产生5-10bp长的RNA引物，提供3’羟基3前导链只需一个RNA引物，后随链的每个岗歧片段需要一个RNA引物Primase引物酶Enzyme that starts a new strand of DNA by making an RNA primer 引物酶合成一个RNA引物，引导DNA 复制的起始leading strand and lagging strandleading strand前导链The new strand of DNA that is synthesized continuouslyduring replicationDNA复制过程中连续合成的新链lagging strand后随链The new strand of DNA which is synthesized in shortpieces during replication and then joined laterDNA复制过程中先合成为短片段，然后连接而形成的新链3.3 RNA引物必须被除去Remove of RNA primers from newly synthesized DNA 3.4 DNA解旋酶在复制叉前方解开DNA双链DNA helicaseEnzyme that unwinds double helical DNA打开DNA 双螺旋结构的酶DNA helicase separate the two stands of the double helix 3.5 单链结合蛋白在DNA复制前能稳定单链结构Single strand binding protein (SSB protein)A protein that keeps separated strands of DNA apart维持DNA分子成为分开的两条单链的蛋白质Binding of single-strand binding protein (SSB) to DNA 3.6 拓扑异构酶除去DNA解链形成的超螺旋DNA topology为什么研究DNA的结构变化？1、是柔性分子具体形状取决于周围的离子，以及与蛋白形成的复合体，螺旋松紧度可变2、松紧受限①环形DNA 双链的相互缠绕数无法改变②当两端固定、分子超长、形成染色质或与其他组分互作时，线形DNA的拓扑异构受限3、与功能相关DNA复制，转录，染色体活动均涉及DNA拓扑结构的变化Supercoiling is the coiling of a coil: a typical phone cord is coiled like a DNAhelix, and the coiled cord can itself coil in a supercoilSupercoiling induced by separating the strands of a helical structureRelaxed and supercoiled plasmid DNAsNegative supercoiling负超螺旋Supercoiling with a left handed or counterclockwise twist左手方向或逆时针方向捻DNA分子时形成的超螺旋There is roughly one supercoil every 200 nucleotides in typical bacterial DNA 在典型的细菌DNA中，大约每200个核苷酸有一个超螺旋Negative (rather than positive) supercoiling helps promote the unwinding and strand separation necessary during replication and transcription 负超螺旋促进解开DNA 双链，在复制和转录过程中必须要解旋Topoisomerase拓扑异构酶功能切断DNA的一条链(topoⅠ)或两条链(topoⅡ)，打断磷酸戊糖骨架分类TopoisomeraseⅡ和TopoisomeraseⅠMechanism of action for topoisomeraseⅠMechanism of action for topoisomeraseⅡDNA gyraseDNA旋转酶An enzyme that introduces negative supercoils into DNA, a member of the typeII topoisomerase family引入负超螺旋的酶，是拓扑异构酶II 家族中的一个成员Action of topoisomerase at the replication fork SummaryDNA polⅠ除去RNA引物，ligase连接DNA拓扑异构酶消除超螺旋SSB蛋白与单链DNA结合解旋酶解链引物酶合成RNA引物前导链连续合成，后随链分段合成双链在一个复制叉上同时合成DNA的合成需要游离3’OHDNA双链需要解开成为单链DNA单链不能稳定存在解链过程中会引入正超螺旋合成的DNA链含有RNA引物DNA合成中的现象及解决方案解决方案现象DNA合成需要的主要组分及其功能1DNA解旋酶DNA helicase在复制叉处解开DNA双链2单链结合蛋白SSB protein与单链DNA结合，阻止DNA褪火3拓扑异构酶gyrase在复制叉的前面切断DNA后再连接DNA，释放由于解链形成的扭力4引物酶primase合成短的RNA引物，提供游离3’-OH，起始DNA的合成5DNA聚合酶ⅢDNA polymerase Ⅲ从引物提供的3’-OH处延长一条新的核苷酸链6DNA聚合酶ⅠDNA polymerase Ⅰ除去RNA引物，用DNA替代7DNA连接酶DNA ligase连接岗歧片段4 DNA 聚合酶(DNA polymerase) 4.1细菌中的三种DNA聚合酶4.1 细菌中的三种DNA聚合酶DNA polymerases in prokaryote (E.coli) Polymerase Number of subunits Function PolⅠ1除去RNA引物，修复DNA PolⅡ1修复DNAPolⅢcore3染色体复制PolⅢholoenzyme9染色体复制功能共有三种活性可拆分为两个部分DNA 聚合酶ⅠDNA polymerase ⅠKlenowfragmentDNA 聚合酶DNA 合成3’-5’外切酶校对separate small domain 5’-3’外切酶DNA修复，除去RNA 引物DNA polymerase Ⅰ: simultaneously remove primer and fill in the gapSubunit composition of E.coli DNA polymerases ⅢholoenzymeD N A p ol y m e r a s e s ⅢCore (核心酶)DNA 合成和校正τ subunit (τ亚基) 连接核心酶和γ复合体γ complex (γ复合体)滑动钳装载机β subunit (β亚基)滑动钳The composition of the DNA polymerase ⅢholoenzymeATP control of sliding DNA clamp loadingStructure of a sliding DNA clampCharacteristics of DNA polymerases in E.coliDNA polymerases in eukaryoteNumber of subunits Probable rolesPolα4DNA复制过程中合成引物Polβ1碱基切除修复Polγ3线粒体DNA复制和修复Polδ2-3DNA复制，核酸和碱基切除修复Polε4DNA复制，核酸和碱基切除修复Polθ1交换过程中的DNA修复5 The mechanism of DNA replication5.1Overview of DNA replication5.2Initiation of DNA replication in bacteria5.3Elongation of DNA replication5.4Termination of DNA replication5.1 Overview of DNA replicationDNA synthesis is continuous on one template strand of DNAand discontinuous on the otherDNA synthesis is continuous on one template strand of DNA and discontinuous on the other DNA synthesis is continuous on one template strand of DNA and discontinuous on the other5.2 Initiation of DNA replication in bacteriaOrigin of replication复制起点Site on a DNA molecule where replication beginsSequences at the Origin of DNA replicationThe structure of replicatorsFunction of the initiator proteins during the initiation DNA replicationE. coli DNA replication begins when initiator proteins bind to ori C, theorigin of replication, causing a short stretch of DNA to unwind E. coli DNA replication begins when initiator proteins bind to ori C, theorigin of replication, causing a short stretch of DNA to unwind大肠杆菌DNA复制的起始起始蛋白与oriC结合引起临近的一小段DNA解链解旋酶和SSB相继结合，DNA复制开始DNA helicase unwinds DNA by binding to the lagging strand template ateach replication fork and moving in the 5'→3' direction along the strand 5.3 Elongation and termination of DNA replication1、DNA解旋酶向右侧移动，DNA全酶与之接触，两个核2、DNA引物酶间歇性地与解旋酶结合，在后随链上合成新的引物心酶分别合成前导链和后随链，SSB保护ssDNA4、已经合成引物的后随链由夹钳装载机组成新的滑动钳3、一个岗歧片段合成完毕后，DNA聚合酶释放滑动钳和DNA5、引物:模板结合体以及滑动钳与DNA聚合酶结合，开始新的岗歧片段合成DNA ligase seals the nick after DNA polymerase I has added the final nucleotideDNA ligase seals the nick after DNA polymerase I has added the final nucleotide 5.4 Termination of DNA replication TerminusRegion on a chromosome where replication finishesCan be hundreds of bases longTelomeres are simples, repeated DNA sequences found atthe ends of eukaryotic chromosomesThe structure and sequence of human telomereTelomere is an essential structure at the end ofchromosomes to stabling a cellTelomerase is a DNA polymerase that does not need an exogenous templateTelomerase is a DNA polymerase that does not need an exogenous templateExtension of the 3' end of the telomere by telomerase solves the end replication problem。
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In early 1970, Temin and Baltimore independently identified the unusual enzyme, reverse transcriptase and won the Nobel Prize in 1975 for their work Their discovery shattered the central dogma of molecular biology which stated the flow of genetic information was from DNA to RNA
向光盛 长江大学医学院
Solution to the Problem: Telomerase
The cell solves this problem by adding DNA sequences to the ends of chromosome: telomeres •Small repeated TG rich (TTAGGG)n sequences Telomere specific proteins, eg. TRF1 & TRF2 bind to the repeat sequence and protect the ends Catalyzed by the enzyme telomerase Telomerase contains protein and RNA •The RNA functions as the template •complementary to the DNA sequence found in the telomeric repeat This allows the telomerase to bind to the 3’ overhang
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The End Problem of Eukaryotic Replication
Do chromosomes get shorte with each replication？？？
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RNA primer near end of the chromosome on lagging strand can’t be replaced with DNA since DNA polymerase must add to a primer sequence.
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向光盛 长江大学医学院
Telomerase and Cancer The presence of telomerase in cancer cells allows them to maintain telomere length while they proliferate
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Switch from initiation to elongation: polymerase α/ primase replaced by polymerase δ
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向光盛 长江大学医学院
Removal of RNA Primers
RNAse HI/FEN1 Dna2/FEN1
Sliding clamps attract histone chaperones
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向光盛 长江大学医学院
The Eukaryotic Replisome
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Eukaryotic DNA replication fork
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向光盛 长江大学医学院
at least 8 DNA polymerases
At least 8 different enzymes
•Different DNA polymerases have different functions in the cell • Rate of DNA synthesis in eukaryotic cells = 50 nt/s ( ~ 1/10 rate of bacterial DNA synthesis)
• Two or three DNA polymerases ( and/or ) are present at each replication fork in eukaryotes.
• Telomeres, the unique sequences at the ends of chromosomes, are added to chromosome by a unique enzyme called telomerase.
向光盛 长江大学医学院
Telomerase and Aging Americans Win Nobel For Research On Aging National Public Radio
Because there is very little telomerase in somatic tissues, older people have shorter telomeres -particularly in actively regenerating tissues such as skin or intestinal ephithelia This has generated a lot of interest in the possibility that telomere length could be tied to aging Telomerase and Aging Americans Win Nobel For Research On Aging -National Public Radio
-Primary cells taken from the body and grown in vitro will divide a few times and then stop. If the gene encoding the catalytic subunit of Telomerase is expressed in these primary cells, they grow for many more divisions. -Proliferating cells in the body (stem cells / germ cells) express telomerase -Cancer cells express telomerase
2015/7/28 向光盛 长江大学医学院
Formation of pre-RC
Origin recognition complex，(ORC）Binding to the replicator ORC recruits Helicase loading proteins : Cdc6 and Cdt1 Helicase Mcm2-7 was recruited.
2015/7/28 向光盛 长江大学医学院
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向光盛 长江大学医学院
Telomerase is composed of both RNA and protein
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向光盛 长江大学医学院
Evidence that shortening of telomeres may be a signal to stop cellular division:
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HIV integration:
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向光盛 长江大学医学院
Reverse Transcriptase
DNA Polymerase Activity •Requires primer with 3’ OH termination •Template either RNA or DNA •Requires Mg++ (or Mn++) •Lacks proof-reading function; high error rate (10-4 errors per base)
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向光盛 长江大学医学院
Summary of eukaryotic DNA replication
•The large DNA molecules in eukaryotic chromosome replicate bidirectionally from multiple origins.
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向光盛
Pre-RC activation: •Pre-Rcs are activated to initiate replication by two protein Kinase, CdK and DdK. •High CdK activity is required for Pre-RC activation. •CdK level is low in G1 phase but high in S,G2 and M phases 长江大学医学院
Activation of pre-RC and formation of replication fork
Cdk regulates the formation and activation of pre-RC by phosphorylation of DNA helicase.
2015/7/28 向光盛 长江大学医学院
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向光盛 长江大学医学院
Section Three
Reverse光盛 长江大学医学院
However, the "Central Dogma" has had to be revised a bit. It turns out that you CAN go back from RNA to DNA, and that RNA can also make copies of itself. It is still not possible to go from Proteins back to RNA or DNA, and no known mechanism has yet been demonstrated for proteins making copies of themselves.