Question

What are the consequences of accumulated DNA damage on the cell cycle? (Your

Instructions

answer should be between 150 to 200 words)

Answer 1

DNA being labile, more prone to damage. Apart from external mutagens, aqueous environment and cellular metabolites make increased chance of strand breakage during replication. Proliferating cells are more vulnerable to DNA damage due to more demands of cellular growth and division.

Exogenus factors of DNAdamage include radiation, diet, environmental chemicals. Endogenous sources include chemical instability , depurination , reactive oxygen species, replication damage etc.

Damages include single strand break , double strand break, interstrand cross links etc.The Double strand breaks are most injurious form of DNA damage as they lead to chromosomal breakage and rearrangement and events which may lead to apoptosis or turminogenesis.Un-repaired DNA damages accumulate in non-replicating cells, such as cells in the brains or muscles of adult mammals, and can cause aging.In replicating cells like cells of lining of colon damage accumilation can give rise to mutation or epigenitic alteration this can be replicated and passed on to subsequent generation of cells .This lead to change in function or regulation of gene expression and can contribute to cancer

Consequences:

• DNA damage in non replicating cells, not repaired and accumulated can lead to aging.
• DNA damage in replicating cells can lead to either apoptosis or cancer.

Based on site of damage:
Replication fork arrest various DNA structure: PREMATURE AGING
Recombination pair: CANCERS
Mismatch repair : COLON CANCER
Nucleoside excision repair : XERODERMA PIGMENTOSUM , COCKAYNE SYNDROME
Base excision repair: CANCERS, COCKAYNE SYNDROME, IMMUNE DEFICIENCY , NEURODEGENERATION