Kinds and Components of Origins:

 

Replicons, a Comparative Account:

 

Species

Genome size (bp)

Replicon numbers

Size of a Replicon

Rate of replication (bp)/min

E.coli

4.6 x 10^6

1

4.6 x ^6

50000 to 60000

Yeast (n=17)

1.4 x 10^7

500

40,000

36,000

Fruit fly (n=4)

1.4 x 10^8

3500

40,000

2800

House fly (n=4)

8.6 x 10^8

4000

45,000

2800

X.laevis (n=)

3.1 x 10^9

15000

200kbp

2500

 

 

 

 

 

Mus musculus

2.6 x 10^9

25000

150kbp

2200

 

 

 

Ori-Elements, Their Size, Binding Proteins, Melting Points, Transcriptional Effects

 

Source of Ori

Size

Binding Proteins

Melting Regions

Transcriptional effects

SV 40

4x5 bp-AT rich

T-antigen,

Hexamer

Palindromes

Stimulates

HSV-1

2x8 bp repeats, AT rich in the center

Gp-ul 9

AT region

-

EBV Ori-P

4x30bp repeats,

Two palindromes,

2x30bp enhancers

 

EBNA-1

-

Enhancers stimulate

Ori-Lyt

2 non-contiguous regions

-

-

One enhancer overlaps the other

BPV

2 noncontiguous regions

E-1

-

Similar to EBV

Mitochondrial Origins:

 

 

 

 

H-strand

Promoter & RNA binding site

D-loop

D-loop

Promotes

L-strand

Palindrome

-

-

Promotes

 

 

DNA replication Inhibitors:

 

Cancer is due to uninhibited cell DNA replication. Use of DNA replication inhibitors is useful in therapy. Isotope labeling protocol and 2-D gel Replicon mapping provide the effect of inhibitors on DNA replication events.

 

DNA elongation inhibitors such as Hydroxyurea, Amphidicololin, and Cytosine arabinoside act at chain elongation level, but ineffective in preventing fork movement. But Mimosine and Ciclopirox olamine (CPX) appear to inhibit initiation at origins. It is found very effective in yeast cells.DNA pol alpha is inhibited by Amphidicolin and its derivative amphidicolin glycine.,

 

DNA Topoisomerases are inhibited Novobiocin, Nalidixic acid, Teniposide, etoposide and 4-9-Acridylamine metanesulfon-m-anisidide,

Sodium butyrate, 3-Aminobenzamide and nicotinamide modify chromatin structure; Coralyne and 5,6-dihydroxycoralyne inhibit Topoisomerase-1.

Dimethylzeylasterone inhibits Topoisomerase subunit II,

 

Some of the antibiotics have been found to act on DNA replication:

Trimethoprim (methatrexate, aminopterin) inhibit dihydrofolate reductase, Hydroxy urea- inhibit ribonucleotide reductase, 5-Ffluorouracil competes with dUMP, Dideoxynucleotide prevent nucleotide oligomerization, Mitomycin crosslinks DNA strands and prevent replication progression, Acridine dyes such as Proflavin, and Ethidiumbromide bind to major groove of DNA and prevent replication, Nalidixic acid binds to Gyrase-A, and Novobiocin acts on Gyrase B,

Rifampicin inhibits RNA pol.