Nucleic acid chemistry na 02

Dr. Aga Syed SameerCSIR Lecturer Department of Biochemistry,Medical College,Sher-I-Kashmir Institute of Medical Sciences, Bemina, Srinagar, Kashmir, 190018. India.

NUCLEIC ACIDSCHEMISTRY

DNA

Polynucleotides

• DNA (DeoxyriboNucleic Acid) is called the genetic material because it contains the genetic information for every cell and tissue in an organism

• DNA is a component of the chromosomes (proteins are the other component)

• By 1950 it was known that the DNA is a polymer of deoxyribonucleotides linked through phosphodiester bonds

• DNA is a linear polymer of nucleoside monophosphates. The backbone of the chain consists of alternating units of phosphate and sugar

• The asymmetry of the nucleoside monophosphate monomers of DNA gives the chain a "polarity"

DNA

• In 1953 James Watson & Francis Crick suggested a model of DNA based on the known structures of nucleotides, on X-ray diffraction patterns that Rosalind Franklin & Maurice Wilkins obtained from DNA fibers, and on the chemical equivalencies noted by Chargaff

Watson & Cricks Model

The salient features of the Watson-Crick model of DNA are as:

• DNA consists of two strands wound around each other in a double-helical structure.

• The two strands are antiparallel, one strand runs in the 3 ׳ 5-׳ direction & the other 5 ׳ 3-׳direction.

• Diameter of double-helix is 2 nm, each turn of helix is 3.4nm with 10 pairs of nucleotides and each pair placed at a distance of about 0.34nm.

• Deoxyxyribose and phosphate forms the backbone of each strand lying on the exterior of the molecule.

Watson & Cricks Model

Two polynucleotide chains are complementary to each other, due to base pairing; i.e., where there is Cytosine in one strand there is Guanine in other as is the case with Adenine and Thymine.

Two strands are held together by H-bonds formed between N-bases of two strands. G links with C by three H-bonds; and A forms two H-bonds with T

The genetic information resides in only one strand called as template or antisense strand and the other is called sense strand because it has same sequence as the mRNA synthesized from the template strand except Uracil is present at Thymine positions.

Watson & Cricks Model

Watson & Cricks Model

Watson & Cricks Model

• Sugar Polynucleotides have unrestricted rotation about most backbone bones (within limits of sterics) with the exception of the sugar ring bond

• This behavior contrasts with the peptide backbone

• Also in contrast with proteins, specific, predictable interactions between bases are often formed: A with T, and G with C

• These interactions can be interstrand, or intrastrand

Sugar phosphate backbone conformation

• Sugar Moiety

• Stability

• N- Base

• Linearity and Complexity

DNA Vs RNA

• Erwin Chargaff in 1950 gave a set of conclusions after studying the DNA molecules from different sources; which may be postulated as below:

The DNA obtained from different species has different base composition.

DNA samples obtained from various organs, tissues or cells of same species, have similar base composition.

Base composition of DNA does not change with the environment, nutrition age or sex of an individual or species.

As in the DNA molecule adenine base pairs with thymine and guanine base pairs with cytosine therefore, the amount of purines

in the DNA is equal to that of pyrimidines i.e., A+G = T+C.

The ratio of A+T / G+C known as the dissymetric ratio, varies greatly from one species of DNA to the other and is a characteristic of that species.

Chargaff’s Rules

Different forms of DNAParameters of Major DNA Helices

Parameters A Form B Form Z Form

Direction of helical rotation Right Right Left

Diameter ~2.6nm ~2.0nm ~1.8nm

Helix pitch 2.8nm 3.4nm 4.5nm

Residues per turn of helix 11 10 12 bp

Helix rise per base pair 0.26nm 0.34nm 0.37nm

Rotation of helix per residue (in degrees) 33 36 -30

Base tilt relative to helix axis (in degrees) 20 6 7

Major groove Narrow and deep Wide and deep Flat

Minor groove Wide & shallow Narrow & deep Narrow & deep

Glycosidic bond Anti Anti Syn for purines

Anti for pyrimidines

Ribose conformation C3׳-endo C2׳-endo

C3׳-endo for purines

C2׳-endo for pyrimidines

Different forms of DNA

Intercalation

• DNA Sequence (of nucleotides)that may be read the same way in either direction

• Since the DNA has doubles helical complementary structure, and the nucleotides always pair in the same way (Adenine (A) with Thymine (T), Cytosine (C) with Guanine (G)), a (single-stranded) sequence of DNA is said to be a palindrome if it is equal to its complementary sequence read backward

• For example, the sequence ACCTAGGT is palindromic because its complement is TGGATCCA, which is equal to the original sequence in reverse complement.

Palindromes

Palindromes

Palindromes

Palindromes Vs Mirror Repeats

Palindromes are sequences of double-stranded nucleic acids with twofold symmetry. In order to superimpose one repeat (shaded sequence) on the other, it must be rotated 180 about the horizontal axis then 180 about the vertical axis, as shown by the colored arrows

A mirror repeat, on the other hand, has a symmetric sequence within each strand. Superimposing one repeat on the other requires only a single 180 rotation about the vertical axis

• Proposed by Francis Crick in 1950s to suggest that there was “the unidirectional flow of genetic information”

• Starts from the DNA and ends in proteins via RNA

• It included three main process:

• Replication: For new DNA synthesis from template DNA

• Transcription: For synthesis of RNA on the information of DNA

• Translation: Synthesis of Protein using information from RNA

Central Dogma

Questions

Next Lecture: RNA