Base excision repair in - PowerPoint Presentation

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Base excision repair in Mycobacterium Tuberculosis

DONE BY : Abeer Mohammad

ALShamrani

ID number : 1601256

Mycobacterium TuberculosisThe causative agent of tuberculosis.Is one of the most widespread bacterial pathogens and infects one-third of the global population

causing 1.3–1.4 million deaths each year

This

bacterium

initially colonizes the mucosal surface of the lower respiratory epithelium

and is subsequently phagocytized by alveolar

macrophages

.

Mycobacterium TuberculosisCircular chromosomesAbout 4,411,529 base pairs

Contains about 4000 genes

The G+C content about 65%

Mycobacterium Tuberculosis During colonization of epithelial cell layers in the nasopharynx, lungs and gastrointestinal tract, and the subsequent infection of deeper tissues, bacteria are exposed to different types of reactive oxygen species (ROS) and reactive nitrogen species (RNS).

macrophages

produce

antimicrobial

factors

reactive oxygen species (ROS)

reactive nitrogen species (RNS)

Mycobacterium Tuberculosis

Types of DNA Damage in M.Tuberculosis

Depending on the specific type of ROS or RNS , various forms of DNA damage arise.

Types of DNA Damage

1- Deamination

2-Oxidation

3- Alkylation

-

An amino group of

cytosine

is removed and baes becomes

Uracil

.

- An amino group of

Adenine

is removed and baes becomes

Hypoxanthine

- An amino group of

Guanine

is removed and baes becomes

Hypoxanthine

An alkyl group (

e.g

CH3

) gets added to bases.

Guanine

oxidize to

8-oxo

-guanine

Types of DNA Repair systemes in M.Tuberculosis1- Base Excision Repair

(BER)

2- Nucleotide Excision Repair

(NER)

3- Mismatch Repair

(MMR)

The M. tuberculosis it contains many of the base excision and nucleotide excision repair genes found in E. coli.

It lacks homologues of mismatch repair pathway genes.

The majority of single-base lesions in

M.tuberculosis

can be repaired by the base excision repair (BER) pathway.

Types of DNA Repair systemes in M.Tuberculosis

Excision Repair

The base excision repair (BER) and the nucleotide excision repair (NER) pathways may play a major role in maintaining the integrity of DNA in these bacteria.

Because of the G + C richness of the genome there is more emphasis on enzymes that are involved in the excision of uracil and the oxidized guanine bases.

Base Excision Repair The BER pathway involves excision of modified bases in DNA by a class of enzymes called

DNA glycosylases

which cleaves the N-

glycosidic

bond between the base and the DNA backbone, generating an AP site.

Glycosylases can be classified as monofunctional or bifunctional:

Monofunctional

enzymes possess glycosylase activity only.

Bifunctional

enzymes also have

lyase activity for cleavage of the DNA backbone at the AP site.

Base Excision RepairVariety of DNA glycosylases for different types of damaged bases.

Oxidation

Alkylation

Deamination

MutM1

MutY

Nei1

Nei2

Nth

Alk

A

Mpg

Taq

A

Udg

B

Nei1

Udg

B

Ung

Base Excision RepairFour step process:1- DNA glycosylase

recognizes specific damage base and cleaves the N-

glycosidic

bond between the damaged base and the

suger

phosphate backbone of the DNA.

2- AP endonuclease

cleave AP sites , which cut the DNA backbone and leave a 3ʹ-hydroxyl and a 5ʹ-deoxyribose phosphate (

dRP

).

3-DNA Plymerase

l fills in the gap by inserting the appropriate nucleotides.4- DNA ligase seals the gap.

Base Excision RepairBER has two subpathways :1-

short-patch repair:

single-nucleotide gaps are filled by the activity of DNA polymerase I and are sealed by DNA ligase .

2-

long- patch repair:

PolA

replaces up the lesion with approximately 2 to 10 nucleotides using the 5ʹ-

dRP

-containing strand as a template

Thank you =)

References:Kurthkoti, K., &

Varshney

, U. (2011). Base excision and nucleotide excision repair pathways in mycobacteria. 

Tuberculosis,

91

(6), 533-543.

Veen, S. V., & Tang, C. M. (2015). The BER necessities: the repair of DNA damage in human-adapted bacterial pathogens. 

Nature Reviews Microbiology,

13(2), 83-94.