Chap 16 Repai n Mutaton Sp11i

the general information and knowledge on molecule biology. the deep introduction about genome relate to the genetics.

Mutations & DNA repairGoals Understand how mutations occur & their effect on cell phenotype Know how mutagens cause mutations Know what mechanisms exists in cells to overcome damage done to their DNA Know how the DNA repair system is able to distinguish between parental DNA strand from mutation carrying strand1

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the general information and knowledge on molecule biology. the deep introduction about genome relate to the genetics.

Mutation Background Mutation - heritable change in gene sequence. Mutation increases genetic variations in a population. Mutations may occur naturally (spontaneous) OR can be introduced by design (induced). Most mutations result from errors in DNA replication or from environmental insults.

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the general information and knowledge on molecule biology. the deep introduction about genome relate to the genetics.

Mutation Causes of Spontaneous mutations Error in DNA replication–Tautomerism –Error in repair mechanism –Replication slippage

Radiation damage–UV rays from sunlight –Radon gas from Uranium depositsMolec Biol Sp’11 3

Bhuta

the general information and knowledge on molecule biology. the deep introduction about genome relate to the genetics.

Mutation

Tautomerism yields; A:C, G:T & T:G pairs

Molec Biol Sp’11

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the general information and knowledge on molecule biology. the deep introduction about genome relate to the genetics.

Replication slippage

Slippage is frequently associated with repeat sequences.

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the general information and knowledge on molecule biology. the deep introduction about genome relate to the genetics.

Mutation Additional causes of spontaneous mutations are: Chemical changes– deamination & depurination

Biological agents– Transposons Note: mutations can only occur if the DNA repair system in the cell fails to ‘fix’ the damage!Molec Biol Sp’11 Bhuta 6

the general information and knowledge on molecule biology. the deep introduction about genome relate to the genetics.

Error correction

DNA polymerase has proof reading ability, which prevents error in replication

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the general information and knowledge on molecule biology. the deep introduction about genome relate to the genetics.

MutationCategories of mutations Point mutations Transitions (e.g. purine to purine) Transversion (e.g. purine to pyrimidine) Mutations involving more than one base generally result from deletion or addition of multiple bases.Molec Biol Sp’11 Bhuta 8

the general information and knowledge on molecule biology. the deep introduction about genome relate to the genetics.

MutagensBase analogs (e.g. FU, BrU) Deaminating agents (e.g. HNO2) Alkylating agents (e.g. EMS) Intercalating agents (e.g. ethidium bromide) Radiation UV light, ionizing radiation (e.g. X-rays)

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the general information and knowledge on molecule biology. the deep introduction about genome relate to the genetics.

Mutation

Deamination A:T A:C C:G U:A

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the general information and knowledge on molecule biology. the deep introduction about genome relate to the genetics.

Mutation

Dimer formation

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the general information and knowledge on molecule biology. the deep introduction about genome relate to the genetics.

MutationA change in genotype (mutation) may result in change(s) in phenotype. Based on the effect on phenotype a mutation may be called: Silent (synonymous change), missense (nonsynonymous change) may also be “read through” type, or nonsense . A special category of mutations are suppression, conditional lethal mutation, etc.Molec Biol Sp’11 Bhuta 12

the general information and knowledge on molecule biology. the deep introduction about genome relate to the genetics.

Are mutations Programmed OR Spontaneous?

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the general information and knowledge on molecule biology. the deep introduction about genome relate to the genetics.

Mutations in EukaryotesResults into either loss of function OR gain of a function. Phenotypic change may occur late (late onset) e.g. delayed onset, late or non-panetrance. It may also be influenced by multiple allelic condition. Some sites in both cell types are prone to frequent mutations (hyper mutation sites).

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the general information and knowledge on molecule biology. the deep introduction about genome relate to the genetics.

DNA repairRepairing of the damage may involve Dir

ect repair of the lesion Excision repair Mismatch repair Nonhomologous end joining (NHEJ) repair

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the general information and knowledge on molecule biology. the deep introduction about genome relate to the genetics.

DNA repair

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