Biochemistry 401G Lecture 32 Andres

Transcription

1 Biochemistry 401G Lecture 32 Andres Lecture Summary: Discuss RNA structure and how the chemical differences between DNA and RNA make DNA the better choice for the storage of genetic information. DNA chromatin structure. Why package DNA within the nucleus? RNA Structure: The basic chemical linkages in RNA and DNA are similar, but the structure of RNA differs from that of DNA in several ways. The additional hydroxyl group in the ribose backbone leads to steric interference that blocks the ability of RNA polymers to form long double helices between complementary strands. Double-helical structures arise in RNA when the strand turns back on itself and base pairing occurs between antiparrallel complementary or quasicomplementary segments of base sequences within the same strand (often only 9-12 bases in length). The helical segments of RNA are less stable than DNA.

2 Why did DNA evolve? RNA molecules can, in principle, fulfill all the cellular functions performed by proteins and DNA. For example, RNA provides structural scaffolding for ribosomes, and RNA enzymes (ribozymes) catalyze a variety of chemical reactions. In addition, RNA can serve as a template for the synthesis of a complementary polynucleotide strand, an essential criterion for the transmission of genetic information. Indeed, numerous viruses carry either single-stranded or double-stranded RNA as their genetic material. The position of proteins as the major catalytic macromolecules can be explained by the greater chemical versatility of 20 amino acid side chains compared to that of the four chemically quite similar nucleic acid bases. However, a different explanation is required to rationalize why DNA co-opted the function of safeguarding and transmitting genetic information. Simply put, DNA is more suitable because it is more stable than RNA. RNA is highly susceptible to base-catalyzed hydrolysis.

3 DNA is organized into specific intracellular structures. Reasons for organization: 1. There are large amounts of DNA in each nucleus. One human chromosome (there are 46 in total) contains x 106 bp (base pairs), and is cm long. Chromosomes are very fragile and subject to shear damage if unprotected. 2. Not all of the DNA is (or should be) available for expression; some is packaged in a manner that makes its genetic information inaccessible. There are several successive layers of organization in eukaryotic DNA.

4 1. The nucleosome consists of four histone molecules (H2A, H2B, H3 and H4) with a strand of double helical DNA wrapped around them. The histones are proteins that are highly conserved across species lines (implies great importance of the protein structure). basic- contain lots of Arg and Lys (positively charged) amino acids, which interact with the DNA via salt bridges. 2. The chromatosome is a nucleosome plus a fifth histone (H1) that holds the structure together. 3. Nucleosomes form higher order structures (100 Angstrom fiber and 300 Angstrom fiber (solenoid)). 4. Additional non-histone proteins are added to help form the chromosome. 5. The result of this organization is chromatin, the name given the complex of genetic material in eukaryotes.

5 6. The chromosome is one very large DNA molecule-- linear in eukaryotes. It has three essential elements. 1. centromere (spindle attachment site during cell division) 2. telomeres (ends) 3. one or (in eukaryotes) many origins of replication. In prokaryotes DNA is also organized. It is double-stranded circular supercoil in a compact structure called the nucleoid, containing various proteins (some histone-like). The intracellular location of the chromosome differs between eukaryotes and prokaryotes. In prokaryotes it is attached to the inner surface of the plasma membrane, but it is in contact with the cytoplasm. In eukaryotes, the chromosomes are in the nucleus, isolated from the potentially damaging chemistry that takes place in the cytoplasm.