MAMMALIAN

ARTIFICIAL
CHROMOSOMES
(MAC)
Mammalian Artificial Chromosomes:

Mammalian artificial chromosome (MAC) is a molecule of characterized

structure containing blends of different cloned or combined
chromosomal components that are exclusively controlled, tried and
advanced as a major aspect of a controlled construction process.

REASONS FOR BUILDING MAC:

1. The main purpose behind building MAC's is consequently to help

our comprehension of how mammalian chromosomes function.
2. A second reason for constructing MACs is that to identify the
sequences responsible for such sex chromosome behavior at
Mitosis and Meiosis.
3. It will also build up our understanding of the requirements for
normal chromosome maintenance, replication and segregation.
4. It could be utilized for transferring genes into cells which could
be advantageous for quality treatment and in the generation of
transgenic creatures.

STRATEGIES FOR CONSTRUCTION OF MAC:

There are two strategies for the construction of MAC which are as
follows:

1. Top-down strategy
2. Build-up strategy
1. Top-down strategy:

The top down strategy uses artificially induced chromosome

truncations as a means to define a minimal chromosome that retains
the mitotic properties of a normal chromosome.
In this, cloned telomeric DNA is utilized to part a characteristic
chromosome into a minichromosome through at least one rounds of
telomeric coordinated chromosome breakage. Minichromosomes has
likewise been created in some lower creatures, including the organic
product fly Drosophila Melanogaster and the parasitic
protozoanTrypanosoma brucei

2. Build-up strategy/Bottom-up approach:

Construction of a MAC utilizing this strategy/approach is like that
utilized for YACs, has been dangerous since out of the three
components considered essential just telomeres have been
basically characterized.
Mammalian telomeric DNA comprises of a repeat of the hexamer
TTAGGG that is recreated by telomerase, a specific turn around
transcriptase.
Cloned telomere repeat have been brought into mammalian cells
and can seed the development of another telomere by healing a
broken chromosome end in a procedure called Telomere-
associated chromosome fragmentation (TACF).
The origin sequences for chromosome origin point successions
happen at each 100 kb, yet most human DNA successions of no
less than 20 kb long can bolster DNA replication when
reintroduced into refined cells on episomal vectors.
No consensus origin sequence has been identified, prompting a
view that lead origin potential may be distinguished at least in
part by epigenetic mechanisms, possibly involving methylation of
CpG dinucleotides.
The mammalian centromere shapes an obvious essential
narrowing and contains very redundant (satellite) DNA that
structures a dense chromatin structure called heterochromatin.
The repeat which is basic to every single mammalian centromere
is -satellite (alphoid) DNA which includes 171 bp monomers
sorted out into chromosome-particular higher request repeatss.
 The measure of alphoid DNA per centromere ranges from 500 kb
to 5 Mb.
A subset of alphoid DNA groupings contact the axle microtubules
at a district called the kinetochore, a DNAprotein complex
noticeable as a trilaminar structure by electron microscopy.
Various proteins with particular confinement at the kinetochore
have been recognized.
CENP-A, a histone H3 variation which might be in charge of
creating a one of a kind chromatin structure at centromeres.
CENP-C, a DNA-authoritative protein, are both situated at the
internal kinetochore plate.
CENP-B ties to a 17 bp theme (CENP-B box) discovered much
of the time in alphoid DNA and are situated inside the basic
driven heterochromatin.
CENP-E is a kinesin-like engine protein found at the external
plate.
REFERENCES:

1. Grimes, B., and Cooke. H. (1998) "Engineering Mammalian

Chromosomes." Human Molecular Genetics 7, Vol 10, 1635-1640.
2. Brown.W. (1992) Mammalian artificial chromosome. Current opinion in genetics
and development .Vol 2,479-486
3. Willard, H. F. (2000) "Genomics and Gene Therapy: Artificial
Chromosomes Coming to Life." Science , 1308-1309.