DNA Repair Types

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Specifically repaires O6-alkylguanines (e.g. O6-Me-dG, O6-Bz-dG) In a stoichiometric response, the O6 alkyl gathering is exchanged to a Cys buildup in the dynamic site. The protein is inactivated and debased. . Direct repair: O6-alkylguanine DNA alkyltransferase (AGT). AGT inhibitor O6-benzylguanine is in clinical trials to be utilized as a part of conjunction with antitumor alkylnitrosoureas.

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DNA Repair Types Direct repair Alkylguanine transferase Photolyase Excision repair Base extraction repair Nucleotide extraction repair Mismatch repair Recombination repair

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Direct repair: O 6 - alkylguanine DNA alkyltransferase (AGT) Directly repaires O 6 - alkylguanines (e.g. O 6 - Me-dG, O 6 - Bz-dG) In a stoichiometric response, the O 6 alkyl gathering is exchanged to a Cys buildup in the dynamic site. The protein is inactivated and debased.

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AGT inhibitor O 6 - benzylguanine is in clinical trials to be utilized as a part of conjunction with antitumor alkylnitrosoureas

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AGT overexpression in tumors makes them impervious to alkylnitrosoureas

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Combination treatment with O 6 - benzylguanine beats tumor imperviousness to alkylnitrosoureas

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Excision Repair Takes favorable position of the twofold stranded (twofold data) nature of the DNA atom. Four noteworthy strides : Recognize harm. Expel harm by extracting some portion of one DNA strand. The subsequent hole is filled utilizing the in place strand as the layout. Ligate the scratch.

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Antiparallel DNA Strands contain the same hereditary data 5' 5' 5' 3' 3' 3' A :: T A :: T A :: T G ::: C G ::: C G T :: A T :: A T :: A 5' 5' 5' 3' 3' 3' Original DNA duplex DNA duplex with one of the nucleotides evacuated Repaired DNA duplex

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X a n t h i n e Base extraction repair (BER) Used for repair of little harmed bases in DNA (AP destinations, methylated bases, deaminated bases, oxidized bases… ) Human BER quality hogg1 is much of the time erased in lung tumor O N H N O H

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Uracil DNA glycosylase expels deaminated C No Me aggregate N H O 2 BER C N H N O N O Cytosine Not ordinarily display in DNA U r a c i l Normal DNA base Not perceived by BER

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Nucleotide Excision Repair Corrects any harm that both bends the DNA atom and adjusts the science of the DNA particle ( pyrimidine dimers, benzo[ a ]pyrene-dG adducts, cisplatin-DNA cross-joins) . Xeroderma pigmentosum is a hereditary issue bringing about flawed NER

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Mismatch Repair Enzymes Nucleotide bungles can be amended after DNA union! Repair of nucleotide confuses: Recognize parental DNA strand (adjust base) and girl strand (off base) Parental strand is methylated: 2. Supplant a segment of the strand containing wrong nucleotide (between the befuddle and a close-by methylated site –up to 1000 nt) G T

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Genetic sicknesses related with imperfect DNA repair Xeroderma Pigmentosum NER Hereditary nonpolyposis MMR colorectal malignancy Cockrayne's syndrome NER Falconi's anemia DNA ligase Bloom's syndrome BER, ligase Lung tumor (?) BER

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Chapter 3. RNA blend (Transcription) Required perusing: Stryer 5 th version p. 129-132, 781-792 (or Stryer 4 th version p. 95-102, 841-849, 851-859)

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Flow of hereditary data DNA RNA Proteins Cellular Action replication interpretation DNA

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C U G U G G•C A•U C•G G•C C•G G•C 5'- U•C•C•C•A•C A•U•U•U-3' RNA is a biopolymer comprising of ribonucleotide units 5' RNA is typically single stranded however can shape fastener structures by collapsing over a similar strand: Loop Double-stranded area (stem) 3'

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Structural contrasts amongst DNA and RNA DNA RNA

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RNA Types mRNA = Messenger RNA; a RNA duplicate of the DNA arrangement (quality) utilized as a layout for protein union tRNA = Transfer RNA; a little RNA that is joined to an amino corrosive which can be added to a developing peptide chain rRNA = Ribosomal RNA; part of ribosomes with reactant and auxiliary function snRNA = Small atomic RNA, required in RNA grafting in eukaryotes

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RNA in E. coli

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2Pi RNA union RNA union includes translating a particular bit of DNA strand into RNA succession RNA polymerases successively add ribonucleotides to the 3' end of a RNA polymer utilizing DNA strand as a layout (5'  3' course) RNA Pol chooses ribonucleotides corresponding to the DNA format and catalyzes the development of new phosphodiester bonds. This procedure is rehashed as the compound moves along the DNA.

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RNA Synthesis: expansion of new NTPs takes after Watson-Crick rules H N 2 NH 2 NH 2 N O N O N NH N HN N O A•U G•C Template base Incoming base G C C G U A A U

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Coding strand 5'… A T G C T G A C T C A… 3' 3'… T A C G A C T G AA G T… 5' 5'- A U G C U G A C U C A… 3' Transcription Non-coding (layout) strand Translation … Met-Ala-Trp-Thr-Ser… Peptide The succession of the RNA transcript is integral to the deciphered DNA strand and is the same as the coding strand