gene structure and mutation

Gene Structure and Mutation

Dyah Ratna BudianiBagian Patologi Anatomi/ Lab Biomedik FK-UNS

Gene ?

Tradisional : suatu segment DNA yang mengkode 1 rantai polipeptida atau 1 molekul RNA fungsional.

Modern :suatu sekuens genomik DNA atau RNA yang esensial untuk 1 fungsi spesifik.

Tipe Gen :1.1. Protein Coding GenesProtein Coding Genes = adalah gen yang ditranskripsi adalah gen yang ditranskripsi

menjadi mRNA dan selanjutnya mengalami translasi mjd menjadi mRNA dan selanjutnya mengalami translasi mjd protein (protein (structural genesstructural genes) ) RNA Polymerase II RNA Polymerase II

2.2. RNA –specifying genesRNA –specifying genes = yang hanya mengalami transkripsi yang hanya mengalami transkripsi tanpa translasi.tanpa translasi.

1. rRNArRNA ((RNA Pol I),RNA Pol I),

2.2. scRNAscRNA RNA Pol II or III)RNA Pol II or III)

3.3. snRNAsnRNA

4.4. t RNA.t RNA.

3.3. Regulatory Genes =Regulatory Genes = gen yang tidak mengalami transkripsi gen yang tidak mengalami transkripsi maupun translasi tetapi merupakan sekuens regulator untuk maupun translasi tetapi merupakan sekuens regulator untuk ekpresi gen (ekpresi gen (untranscribed sequencesuntranscribed sequences))

All living organism, termasuk juga virus memiliki materi genetik : deoxyribonucleic acid (DNA).

DNA polimer dari : gula (deoksi ribosa), basa nitrogen dan pospat nukleotida

DNA berupa polynukleotida(polimer dari nukleotida).

Basa nitrogen terdiri atas 2 Purin [ yaitu : Adenin (A)dan Thymine(T) ] dan 2 Pirimidin [ yaitu : Guanine(G) dan Cytosine(C) ]

All living organism, termasuk juga virus memiliki materi genetik : deoxyribonucleic acid (DNA).

DNA polimer dari : gula (deoksi ribosa), basa nitrogen dan pospat nukleotida

DNA berupa polynukleotida(polimer dari nukleotida).

Basa nitrogen terdiri atas 2 Purin [ yaitu : Adenin (A)dan Thymine(T) ] dan 2 Pirimidin [ yaitu : Guanine(G) dan Cytosine(C) ]

Schematic representation of anti-parallel Schematic representation of anti-parallel stucture of double-stranded DNA.stucture of double-stranded DNA.

Keterangan :

OH = HIDROKSIL, dR= doksiribosa, P= Phospat, A= Adenine, G=Guanine; T=Thymine, C=Cytosine; ● ● ● = strong hidrogen bound;

● ● = weak hidrogen bound

DOGMA GENETIK :DOGMA GENETIK :

DNA DNA RNA PROTEIN

REPLIKASITRANSKRIPSI TRANSLASI

NH3

COOH

splicing

Maturasi, Folding,Glikosilasi, sorting dan targeting

mRNA

Struktur genes :Struktur genes :

Terdiri atas :

transcribed & non transcribed partstranscribed & non transcribed parts

Flaking region,introns, spesific sequens for spesific signals, initiation, tempo & timing regulatory of the transcription process. Regulatory sequences promote : promoter region yang teridi atas :

TATA box(19-27bp,control atau menentukan start point of transcription)

CAAT box dan GC box orientasi dan kontrol inisiasi tempat melekatnya RNA Polymerase.

Cap site= transcription initiation site,

exons

end = termination site

Poly Adenilasi(poly A)

Cap site= transcription initiation site,

exons

end = termination site

Poly Adenilasi(poly A)

gene structure

(a). Schematic structure of a typical eukaryotic protein-coding gene. Note that, by convention, the 5' end is at the left.

(b). Schematic structure of an induced prokaryotic operon (Slide berikut)

(b) Schematic structure of an induced prokaryotic operon. Genes A and B are protein-coding genes and are transcribed into a single messenger RNA. The repressor gene encodes a repressor protein, which binds to the operator and prevents the transcription of the structural genes by blocking the movement of the RNA polymerase. The operator is a DNA region with at least 10 bases, which may overlap the transcribed region of the genes in the operon. By binding to an inducer (a small molecule), the repressor is converted to a form that cannot bind to the operator. The RNA polymerase can then initiate the transcription of the genes A and B in the operon (see Lewin 1990). In both (a) and (b), the regions are not drawn according to scale.

RNA –SPECIFYING GENES

REGULATORY GENES

Replicator genes : which specify sites for initiation & termination of DNA Replication.

Recombinator genes : which provide spesific recognition site for recombination enzymes.

Segregator genes : spesific site for attachment of the chromosome to segregation machinenary during mitosis /meiosis.

Attachment site for protein, hormon and others molecules

Mutasi gen :

Mutasi terjadi karena kesalahan penyalinan sekuen DNA selama replikasi.

Mutasi : substitusi, insersi, delesi dan inversi Substitusi : transisi ( subtitusi : A G (purin) or TC

(pirimidin). Substitusi : tranversi ( subtitusi : T G or(AC)

purine ke pirimidin atau sebaliknya Inversi rotasi 180°(lihat gambar berikut)

Tipe substitusi

Synonimous = jika tidak merubah asam amino

Missense = jika mutasi merubah aa Non sense = jika mutasi menyebabkan

adanya terminasi/stop kodon.

Crossing over & deletion of DNA sequence

Generation of duplications or deletions by slipped-strand mispairing between contiguous repeats (underlined). Small arrows indicate direction of DNA synthesis. Do is indicate base pairing.

(a) A two-base slippage in a TA repeat during DNA replication. Slippage in the 3' 5' direction results in the insertion of one TA unit (left panel). Slippage in the other direction results in the deletion of one repeat unit (right panel). The deletion shown in the right panel results from excision. of the unpaired repeat unit (asterisks) at the 3' end of the growing strand, presumably by the 3' 5' exonuclease activity of DNA polymerase.

(b) A two-base slippage in a TA repeat in nonreplicating DNA. Mismatched regions form single-stranded loops, which may be targets of excision and mismatch repair. The outcome (a deletion or an insertion) will depend on which strand is excised and repaired and which strand is used as template in the DNA repair process. Modified from Levinson and Gutman (1987).