DNA Organization and Repair PDF

# DNA organization - Histones are positively charged (cationic) proteins that are used to wrap up negatively charged DNA polymers. - Histones are rich in positively charged amino acids: Lysine and Arginine, and also with Mg2+. - There are following types of Histones: H1, H2A, H₂B, H3, H<...

# DNA organization - Histones are positively charged (cationic) proteins that are used to wrap up negatively charged DNA polymers. - Histones are rich in positively charged amino acids: Lysine and Arginine, and also with Mg2+. - There are following types of Histones: H1, H2A, H₂B, H3, H₄. - 2 units of each: H₂A, H₂B, H3 and H₄ histones aggregate together to make a structure called *Octamer* (because it has 8 units total). - A diagram shows how H1, H2A, H2B, H3 and H4 are joined to make an octamer. - DNA double helix wraps around each octamer twice and then moves to the next octamer. - Each octamer with DNA wrapped twice around it is called a *Nucleosome*. - Portion of DNA that is in between two neighboring nucleosomes is called *Linker DNA*. - This portion of DNA is associated with H1 histones. - H1 histones are most species specific and also organ specific molecules out of all histones. - This structure that looks like a chain of beads is called *Nucleofibrile*. DNA helix itself is 2 nm wide. *Nucleofibrile* is 10 nm wide. - *Nucleofibrile* itself is wrapped around a cylindrical shape protein called *Nucleoplasmin*. - When *Nucleotibrile* wraps around *nucleoplasmin*, *nucleoplasmin* moves out and leaves long coil made of *nucleotibrile*. - This coil structure is now 30 mm wide, and it is called *Nucleofilament*. - *Nucleofilament* is wrapped (or coiled) around a long protein called a *Scaffolding Protein*. - When DNA is open and is made of just double helix it is called *Euchromatin*. - Highly condensed portions of DNA is called *Heterochromatin*. - *Euchromatin* is made of portions of the DNA that are being currently transcribed (*genes* that are being expressed). - A note about nucleosomes: because each nucleosome has 8 histone molecules, and histones are proteins, each nucleosome has 8 amino ends of polypeptides protruding outwards. - It is chemical modification of these amino ends that can affect stability of the nucleosome. These are the usual types of the chemical modifications of these amino ends: - Methylation - Phosphorilation - Acetylation - Covalent linkage - ADP ribosylation - After DNA replication, all octamers from the parental DNA go to one of the daughter DNAs and the second daughter DNA has to make its own octamers. # DNA Repair - Normally, approximately after every 1000 nucleotides, DNA has GATC sequence where Adenine is methylated. - When DNA replication is completed, each new double helix is semimethylated: parental strand is methylated (as it was already methylated before replication even started) and new strand is not yet methylated. - DNA *Mismatch repair system* consists of several proteins that come into play during G2 phase of cell cycle. - This protein complex scans new DNA double helixes for nucleotide pair mismatch. - If a mismatch is found, this repair system first identifies which strand is parental strand and which one is new because error has to be corrected in the new strand. - Methylation of parental strand serves as a chemical marker in this case. - After identifying the mismatch and the new strand: *Mismatch repair system* locates nearest GATC sites proximal and distal from the mismatch point and cuts out the whole new DNA segment between those two GATC areas. - Then DNA polymerase comes in and elongates DNA from 5' to 3' direction and in the end DNA Ligase connects 3' end of the chain to th 5' end of the rest of the chain. - Primary gene in this DNA mismatch repair system is *MSH-2 gene*. - Damage in *MSH-2 gene* often results in *Hereditary Non-Polyposis Colon Cancer*. ## Another type of DNA repair system is called *Base Excision Repair*. - This repair takes place in *A.P. Sites* of DNA chain. - *A.P.* Sites are in two ways usually: - Purines (adenine and guamine) have tendency to spontaneously fall out from their place in the nucleotides, leaving sugar-phosphate backbone intact. - Some Nitrates and Nitrites can sometimes cause deamination of cytosine, turning it into Uracil. - When this aberrant base is detected in DNA chain an enzyme called *Glycosylase* cuts it out, again leaving the A.P. site.