Mutasi Gen

MUTASI GEN(PROKARIOT)Sri Agung Fitri Kusuma

DEFINISIWild type

mutanGenotipMutagen

Mutasi

PENGARUH MUTASI TERHADAP AKTIVITAS PROTEIN

FENOTIPE PADA GENETIKA BAKTERIAUXOTROPHIC MUTANTS

RESISTANT MUTANTS

Types of DNA ChangeThe simplest mutations are base changes, where one base is converted to another. These can be classified as either: --transitions, where one purine is changed to another purine (A -> G, for example), or one pyrimidine is changed to another pyrimidine (T -> C, for example). transversions, where a purine is substituted for a pyrimidine, or a pyrimidine is substituted for a purine. For example, A -> C.

Another simple type of mutation is the gain or loss f one or a few bases.Larger mutations include insertion of whole new sequences, often due to movements of transposable elements in the DNA or to chromosome changes such as inversions or translocations.Deletions of large segments of DNA also occurs.

TIPE MUTASI

Missense mutation Nonsense mutation Insertion Deletion Duplication Frameshift mutation Repeat expansion

Missense Mutation This type of mutation is a change in one DNA base pair that results in the substitution of one amino acid for another in the protein made by a gene.

Nonsense Mutation A nonsense mutation is also a change in one DNA base pair. Instead of substituting one amino acid for another, however, the altered DNA sequence prematurely signals the cell to stop building a protein. This type of mutation results in a shortened protein that may function improperly or not at all.

Insertion An insertion changes the number of DNA bases in a gene by adding a piece of DNA. As a result, the protein made by the gene may not function properly.

Deletion A deletion changes the number of DNA bases by removing a piece of DNA. Small deletions may remove one or a few base pairs within a gene, while larger deletions can remove an entire gene or several neighboring genes. The deleted DNA may alter the function of the resulting protein(s).

Duplication A duplication consists of a piece of DNA that is abnormally copied one or more times. This type of mutation may alter the function of the resulting protein.

Frameshift Mutation This type of mutation occurs when the addition or loss of DNA bases changes a gene's reading frame. A reading frame consists of groups of 3 bases that each code for one amino acid. A frameshift mutation shifts the grouping of these bases and changes the code for amino acids. The resulting protein is usually nonfunctional. Insertions, deletions, and duplications can all be frameshift mutations.

Repeat Expansion Nucleotide repeats are short DNA sequences that are repeated a number of times in a row. For example, a trinucleotide repeat is made up of 3-base-pair sequences, and a tetranucleotide repeat is made up of 4-base-pair sequences. A repeat expansion is a mutation that increases the number of times that the short DNA sequence is repeated. This type of mutation can cause the resulting protein to function improperly

MUTAGEN & DNA REPAIR

PENYEBAB MUTASIBase analogs kesalahan replikasi oleh DNA polimeraseFaktor lingkungan : panas, radiasi Zat kimia : alkilasi, deaminasi, zat penginterkalasi, oksigen reaktif

DNA REPAIR SPECIFIC REPAIR GENERAL REPAIR

SPECIFIC REPAIR

DEAMINASI BASAHilangnya gugus amino dari adenine, cytosine dan guanineSpontan atau karena zat kimia tertentu (deaminating agent)Deaminating agent : hydroxylamine : deaminasi cytosine (GC AT), in vitroBisulfite : deaminasi cytosine pada ssDNA, site directed mutagenesis Nitrous acid : deaminasi adenine, cytosine dan guanine (GC AT, AT GC), in vitro dan in vivoRepair Deaminasi basa : DNA glikosilase AP endonuklease

Deaminasi basa oleh Nitrous acid

Repair Deaminasi Basa

Deaminasi 5-methylcytosineMutasi menghasilkan timinPada E. coli biasanya terjadi pada 5CCWGG3/ 3GGWCC5 (W =AT atau TA)GT mismatchRepair : vsr endonuklease, Vsr (endonuklease) berikatan dgn mismatch TGPemotongan setelah T pada urutan 5CmCAGG3/3GGTTC5

OKSIGEN REAKTIFBentuk : radikal superoksida, hidrogen peroksida, radikal hidroksilPada bakteri : superoksida dismutase, katalase, peroksida reduktase8-oxoG (GO) : mutagenic agent, oxdized 7,8_dihydro-8-oxoguanine , MISPAIR DENGAN ADENINERepair untuk 8-oxoG (GO) : gen mutmutM : DNA glycosylase (remove 8 oxo G) AP endonucleasemutY : DNA glycosylase (remove A)mutT : mencegah 8-oxoG masuk ke DNA

Sistem Repair Gen mut

ALKILASIPenambahan gugus alkil (CH3, CH3CH2, etc)Oleh zat kimia ethyl methanasulfonate (EMS), methyl methanesulfonate (MMS), nitrosoguanidineRepair : N-glikosilase spesifik, Ap endonukleaseMetiltransferase (repair alkilasi pada karbon 06 (guanin) dan karbon 04 (timin) )Adaptive respoonse

Adaptive Response

Dimer Pirimidin UV irradiation Repair :Photoreactivation : pholyaseN-glikosilase

Tipe Dimer Pirimidin

Repair Dimer Pirimidin

GENERAL DNA REPAIR MECHANISMSMethyl-directed mismatch repair (mutS, mutL dan mutH)Nucleotide excision repairPostreplication/ recombination repair (recA)SOS inducible repair (lexA, recA, umuDC)

Methyl-directed Mismatch Repair

Nucleotide Excision Repair