‫ﻣﺮﺍﺣﻞ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ‪DNA‬‬

‫ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ‪ DNA‬ﺭﺍ ﻣﻲﺗﻮﺍﻥ ﺑﻪ ﺳﻪ ﻣﺮﺣﻠﻪ ﺗﻘﺴﻴﻢ ﻛﺮﺩ‪:‬‬

‫‪ .۱‬ﻣﺮﺣﻠﻪ ﺁﻏﺎﺯ )‪ :(Initiation phase‬ﺷﺎﻣﻞ ﺷﻨﺎﺳﺎﻳﻲ ﻣﺒﺪﺃ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ‪ ،‬ﺗﺸﻜﻴﻞ ﻛﻤﭙﻠﻜﺲ ﺷﺮﻭﻉ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﻳﺎ‬

‫ﺭﻳﭙﻠﻲﺯﻭﻡ ﻭ ﺍﺿﺎﻓﻪ ﺷﺪﻥ ﭼﻨﺪ ﻧﻮﻛﻠﺌﻮﺗﻴﺪ ﺍﻭﻟﻴﻪ ﺍﺳﺖ‪.‬‬

‫‪ .۲‬ﻣﺮﺣﻠﻪ ﻃﻮﻳﻞ ﺷﺪﻥ )‪ :(Elongation phase‬ﻓﺮﺁﻳﻨﺪ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﺑﻪ ﺻـﻮﺭﺕ ﭼﺮﺧـﻪﺍﻱ ﺍﺩﺍﻣـﻪ ﭘﻴـﺪﺍ ﻣـﻲﻛﻨـﺪ ﻭ‬

‫ﻧﻮﻛﻠﺌﻮﺗﻴﺪﻫﺎ ﺩﺭ ﺟﻬﺖ ‪ 5′‬ﺑﻪ ‪ 3′‬ﺍﺿﺎﻓﻪ ﺷﺪﻩ‪،‬ﭘﻠﻲﻣﺮﻳﺰﺍﺳﻴﻮﻥ ﺭﺷﺘﻪ ﭘﻠﻲﻧﻮﻛﻠﺌﻮﺗﻴﺪﻱ ﺍﺩﺍﻣﻪ ﻣﻲﻳﺎﺑﺪ‪.‬‬

‫‪ .۳‬ﻣﺮﺣﻠﻪ ﭘﺎﻳﺎﻥ )‪ :(Termination phase‬ﻛﻤﭙﻠﻜﺲ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﻳﺎ ﺭﻳﭙﻠﻲﺯﻭﻡ ﺟﺪﺍ ﻣﻲﺷـﻮﺩ ﻭ ﺳـﻨﺘﺰ ﺭﺷـﺘﻪﻫـﺎﻱ‬

‫ﺟﺪﻳﺪ ﭘﺎﻳﺎﻥ ﻣﻲﻳﺎﺑﺪ‪.‬‬

‫ﺍﻭﻟﻴﻦ ﻗﺪﻡ ﺩﺭ ﻣﺮﺣﻠﻪ ﺷﺮﻭﻉ ﻳﺎ ﺁﺧﺮ ﻫﻤﺎﻧﻨﺪﺳـﺎﺯﻱ ﺷﻨﺎﺳـﺎﻳﻲ ﻋﻤـﻞ ﻣﺒـﺪﺃ ﻫﻤﺎﻧﻨﺪﺳـﺎﺯﻱ ‪ OriC‬ﺩﺭ ﺑـﺎﻛﺘﺮﻱ‬

‫‪ E.coli‬ﺑﻪ ﻭﺳﻴﻠﻪ ﭘﺮﻭﺗﺌﻴﻦ ‪ dnaA‬ﻭ ﺍﻳﺠﺎﺩ ﺳﻮﭘﺮﻫﻠﻴﻜﺲ ﻣﻨﻔﻲ ﻭ ﻓﺮﻡ ‪ Z – DNA‬ﺍﺳﺖ ﻛﻪ ﺣﺎﻟﺖ ﻧﺎﭘﺎﻳﺪﺍﺭﻱ ﺍﻳﺠﺎﺩ‬

‫ﻛﺮﺩﻩ ﻭ ﺑﻪ ﻧﺎﺣﻴﻪ ﻏﻨﻲ ﺍﺯ ‪ A‬ﻭ ‪ T‬ﺑﺎ ﺩﻭ ﭘﻴﻮﻧﺪ ﻫﻴﺪﺭﻭﮊﻧﻲ ﺿﻌﻴﻒ ﻓﺸﺎﺭ ﻭﺍﺭﺩ ﻣﻲﻛﻨﺪ‪ ،‬ﺳـﭙﺲ ﺗﻮﺳـﻂ ‪dnaC – dnaB‬‬

‫ﺷﻨﺎﺳﺎﻳﻲ ﺷﺪﻩ ﻭ ‪ dnaB‬ﺑﺎ ﻓﻌﺎﻟﻴﺖ ﻫﻠﻴﻜﺎﺯﻱ ﺩﻭ ﺭﺷﺘﻪ ‪ DNA‬ﺭﺍ ﻛﺎﻣ ﹰ‬

‫ﻼ ﺍﺯ ﻫﻢ ﺑﺎﺯ ﻣﻲﻛﻨﺪ‪ ،‬ﭘﺲ ﺍﺯ ﺁﻥ ﭘﺮﻭﺗﺌﻴﻨﻬﺎﻱ ‪SSB‬‬

‫ﺑﻪ ﺭﺷﺘﻪﻫﺎﻱ ﻣﻨﻔﺮﺩ ‪ DNA‬ﻣﺘﺼﻞ ﺷﺪﻩ ﻭ ﺍﻳﻦ ﺭﺷﺘﻪﻫﺎ ﺭﺍ ﺍﺯ ﻫﻢ ﺑـﺎﺯ ﻧﮕـﻪ ﻣـﻲﺩﺍﺭﻧـﺪ‪ ،‬ﺳـﭙﺲ ﭘﺮﺍﻳﻤـﺎﺯ ﻭ ﭘﺮﻭﺗﺌﻴﻨﻬـﺎﻱ‬

‫‪ n ′′, n ′, n‬ﻭ ‪ I‬ﺑﻪ ﻣﺠﻤﻮﻋﻪ ﺍﺿﺎﻓﻪ ﻣﻲﺷﻮﻧﺪ ﺗﺎ ﻛﻤﭙﻠﻜﺲ ﭘﺮﺍﻳﻤﻮﺯﻭﻡ ﺩﺭ ﻧﺎﺣﻴﻪ ﭼﻨﮕـﺎﻝ ﻫﻤﺎﻧﻨﺪﺳـﺎﺯﻱ ﺗـﺸﻜﻴﻞ ﺷـﻮﺩ‪.‬‬

‫ﭘﺮﺍﻳﻤﺎﺯ ‪ RNA‬ﺁﻏﺎﺯﮔﺮ ﺭﺍ ﺩﺭ ﺍﺑﺘﺪﺍﻱ ﺭﺷﺘﻪ ﺭﺍﻫﻨﻤﺎ ﻭ ﺍﺑﺘﺪﺍﻱ ﻗﻄﻌﺎﺕ ﺍﻭﻛﺎﺯﺍﻛﻲ ﻣﻲﺳﺎﺯﺩ ﻭ ﺍﻧﺘﻬﺎﻱ ‪ 3′ − OH‬ﻣـﻮﺭﺩ ﻧﻴـﺎﺯ‬

‫‪ DNA‬ﭘﻠﻲﻣﺮﺍﺯ ‪ III‬ﺭﺍ ﻓﺮﺍﻫﻢ ﻣﻲﻛﻨﺪ‪ .‬ﺩﻭ ﻣﻮﻟﻜﻮﻝ ‪ DNA‬ﭘﻠﻲﻣﺮﺍﺯ ‪ III‬ﻭ ﭘﺮﻭﺗﺌﻴﻦ ‪ rep‬ﺑﻪ ﻣﺠﻤﻮﻋﻪ ﺍﺿﺎﻓﻪ ﺷـﺪﻩ ﻭ‬

‫ﺭﻳﭙﻠﻲﺯﻭﻡ ﺗﺸﻜﻴﻞ ﻣﻲﺷﻮﺩ ﻭ ﺍﺯ ﺁﻧﺠﺎﻳﻲ ﻛﻪ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﺩﻭﺳﻮﻳﻪ ﻳـﺎ ﺩﻭﺟﻬﺘـﻪ ﺍﺳـﺖ ﺩﻭ ﺭﻳﭙﻠـﻲﺯﻭﻡ ﺑـﺎ ﭼﻬـﺎﺭ ‪DNA‬‬

‫ﭘﻠﻲﻣﺮﺍﺯ ﻭﺍﺭﺩ ﻋﻤﻞ ﻣﻲﺷﻮﻧﺪ‪ .‬ﺩﺭ ﻣﺤﻞ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ‪ ،‬ﺩﻭ ﺭﺷﺘﻪ ‪ DNA‬ﺷﺒﻴﻪ ﺩﻭ ﺷﺎﺧﻪ ﭼﻨﮕﺎﻝ ﻣﻲﺷـﻮﻧﺪ ﻭ ﺑـﻪ ﻫﻤـﻴﻦ‬
‫ﺩﻟﻴﻞ ﺑﻪ ﺁﻥ ﭼﻨﮕﺎﻝ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﻳﺎ ‪ Replication fork‬ﻣﻲﮔﻮﻳﻨﺪ‪ .‬ﻳﻚ ‪ DNA‬ﭘﻠﻲﻣﺮﺍﺯ ﺭﺷﺘﻪ ﺭﺍﻫﻨﻤﺎ ﺭﺍ ﺑﻪ ﺻـﻮﺭﺕ‬

‫ﭘﻴﻮﺳﺘﻪ ﻭ ﻣﺪﺍﻭﻡ ﻭ ‪ DNA‬ﭘﻠﻲﻣﺮﺍﺯ ﺩﻳﮕﺮ ﺭﺷﺘﻪ ﺗﺎﺧﻴﺮ ﺭﺍ ﺑﻪ ﺻﻮﺭﺕ ﮔﺴﺴﺘﻪ ﻭ ﺑﺎ ﺗﺸﻜﻴﻞ ﻗﻄﻌـﺎﺕ ﺍﻭﻛـﺎﺯﺍﻛﻲ ﺑـﻪ ﻃـﻮﻝ‬

‫‪ ١٠٠٠‬ﺗﺎ ‪ ٢٠٠٠‬ﻧﻮﻛﻠﺌﻮﺗﻴﺪ ﺳﻨﺘﺰ ﻣﻲﻛﻨﺪ‪ .‬ﺑﺮﺍﻱ ﺍﻳﻨﻜﻪ ﺩﺭ ﻫﻨﮕﺎﻡ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﺭﺷﺘﻪ ﺗﺎﺧﻴﺮ‪ ،‬ﺁﻧﺰﻳﻢ ‪ DNA‬ﭘﻠﻲﻣﺮﺍﺯ ‪III‬‬

‫ﺩﺭ ﻫﺮ ﺑﺎﺭ ‪ ١٠٠٠‬ﺗﺎ ‪ ٢٠٠٠‬ﻧﻮﻛﻠﺌﻮﺗﻴﺪ ﺑﻪ ﻋﻘﺐ ﺑﺮﻧﮕﺮﺩﺩ ﻭ ﺳﺮﻋﺖ ﻋﻤﻞ ﺁﻥ ﻛﺎﻫﺶ ﻧﻴﺎﺑﺪ‪ ،‬ﺭﺷﺘﻪ ﺗﺎﺧﻴﺮ ﺩﺭ ﻣﺤﻞ ﭼﻨﮕﺎﻝ‬

‫‪( 5′ → 3′) 3′‬‬ ‫ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﺗﺎ ﻣﻲﺧﻮﺭﺩ‪ ،‬ﺑﻪ ﻃﻮﺭﻱ ﻛﻪ ﺩﺭ ﺍﻳﻦ ﻣﺤﻞ ﻫﺮ ﺩﻭ ﺭﺷﺘﻪ ﺭﺍﻫﻨﻤﺎ ﻭ ﺗﺎﺧﻴﺮ ﺩﺭ ﺟﻬـﺖ ‪ 5′‬ﺑـﻪ‬

‫ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﻣﻲﺷﻮﻧﺪ ﻭ ﺩﻭ ﺁﻧﺰﻳﻢ ‪ DNA‬ﭘﻠﻲﻣﺮﺍﺯ ‪ III‬ﺩﺭ ﻛﻨﺎﺭ ﻳﻜﺪﻳﮕﺮ ﻗﺮﺍﺭ ﻣﻲﻳﮕﺮﻧﺪ ﻭ ﺑﻪ ﻃﻮﺭ ﻫﻤﺰﻣﺎﻥ ﻛﺎﺭ ﺧﻮﺩ ﺭﺍ‬

‫ﺍﻧﺠﺎﻡ ﻣﻲﺩﻫﻨﺪ‪ .‬ﻭﺟﻮﺩ ﭘﺮﻭﺗﺌﻴﻦ ‪ rep‬ﺟﻬﺖ ﻫﻤﺎﻫﻨﮓ ﻛﺮﺩﻥ ﺳﺮﻋﺖ ‪ DNA‬ﭘﻠﻲﻣﺮﺍﺯ ‪ III‬ﺑﺎ ﺳﺮﻋﺖ ﺑﺎﺯ ﺷﺪﻥ ﻣﺎﺭﭘﻴﭻ‬

‫ﺩﻭﺭﺷﺘﻪﺍﻱ ‪ DNA‬ﺿﺮﻭﺭﻱ ﺍﺳﺖ‪ .‬ﻫﻤﭽﻨﻴﻦ ﻭﺟﻮﺩ ﺗﻮﭘﻮﺍﻳﺰﻭﻣﺮﺍﺯ ‪ I‬ﻭ ‪ II‬ﺑﺮﺍﻱ ﺗﻨﻈﻴﻢ ﭘﻴﭽﻬﺎﻱ ‪ DNA‬ﻻﺯﻡ ﺍﺳﺖ‪ ،‬ﺯﻳﺮﺍ‬

‫ﭘﻴﭽﻬﺎﻱ ‪ DNA‬ﺑﻪ ﺗﺪﺭﻳﺞ ﺩﺭ ﺟﻠﻮ ﻓﺸﺮﺩﻩ ﻣﻲﺷﻮﻧﺪ ﻭ ﺍﻳﻦ ﻓﺸﺮﺩﻩ ﺷﺪﻥ ﭘﻴﭽﺸﻬﺎ ﻣﺎﻧﻊ ﭘﻴﺸﺮﻓﺖ ﻛﻤﭙﻠﻜﺲ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ‬

‫ﺩﺭ ﻃﻮﻝ ﻣﻮﻟﻜﻮﻝ ‪ DNA‬ﻣﻲﺷﻮﺩ‪ DNA .‬ﭘﻠﻲﻣﺮﺍﺯ ‪ III‬ﻧﻮﻛﻠﺌﻮﺗﻴﺪﻫﺎ ﺭﺍ ﻃﺒﻖ ﻗﺎﻧﻮﻥ ﺑﺎﺯﻫﺎﻱ ﻣﻜﻤﻞ ﻭﺍﺗﺴﻮﻥ – ﻛﺮﻳﻚ ) ‪A‬‬

‫ﺑﺎ ‪ T‬ﻭ ‪ C‬ﺑﺎ ‪ ( G‬ﻣﻘﺎﺑﻞ ﺭﺷﺘﻪ ﺍﻟﮕﻮ ﻳﺎ ﻗﺎﻟﺐ ﻗﺮﺍﺭ ﺩﺍﺩﻩ ﻭ ﺑﻴﻦ ﺁﻧﻬﺎ ﭘﻴﻮﻧﺪ ﻓﺴﻔﻮﺩﻱﺍﺳﺘﺮ ﺑﺮﻗﺮﺍﺭ ﻣﻲﻛﻨـﺪ‪ .‬ﺗـﺸﻜﻴﻞ ﭘﻴﻮﻧـﺪ‬

‫ﻓﺴﻔﻮﺩﻱﺍﺳﺘﺮ ﺣﺎﺻﻞ ﺣﻤﻠﻪ ﻫﺴﺘﻪﺧﻮﺍﻩ ﮔﺮﻭﻩ ﻓﺴﻔﺎﺕ ﻧﻮﻛﻠﺌﻮﺗﻴﺪ ﻭﺍﺭﺩ ﺷﺪﻩ ﺑﻪ ﻋﺎﻣﻞ ‪ 3′ − OH‬ﺭﺷﺘﻪ ﺩﺭ ﺣﺎﻝ ﺳﺎﺧﺖ‬

‫ﻣﻲﺑﺎﺷﺪ‪ .‬ﺩﺭ ﺍﻳﻦ ﻣﺮﺣﻠﻪ ﭘﻴﺮﻭﻓﺴﻔﺎﺕ ﺁﺯﺍﺩ ﻣﻲﺷﻮﺩ ﻛﻪ ﺑﻪ ﻭﺳﻴﻠﻪ ﺁﻧﺰﻳﻢ ﭘﻴﺮﻭﻓﺴﻔﺎﺗﺎﺯ ﻫﻴﺪﺭﻭﻟﻴﺰ ﻭ ﺑﻪ ﺩﻭ ﻣﻮﻟﻜﻮﻝ ﻓﺴﻔﺎﺕ ﻭ‬

‫ﺍﻧﺮﮊﻱ ﺗﺒﺪﻳﻞ ﻣﻲﺷﻮﺩ‪ .‬ﺍﻧﺮﮊﻱ ﺣﺎﺻﻠﻪ ﺗﺎﻣﻴﻦﻛﻨﻨﺪﻩ ﺍﻧﺮﮊﻱ ﻣـﻮﺭﺩ ﻧﻴـﺎﺯ ﺑـﺮﺍﻱ ﻫﻤﺎﻧﻨﺪﺳـﺎﺯﻱ ﻣـﻲﺑﺎﺷـﺪ‪ .‬ﺩﺭ ﺍﻳـﻦ ﻣﺮﺣﻠـﻪ‬

‫ﻳﻮﻥ ‪ M g 2+‬ﻻﺯﻡ ﺍﺳﺖ‪ .‬ﺩﻗﺖ ﻋﻤﻞ ﺁﻧﺰﻳﻢ ‪ DNA‬ﭘﻠﻲﻣﺮﺍﺯ ‪ III‬ﺑﺴﻴﺎﺭ ﺑﺎﻻ ﺍﺳﺖ ﻭﻟﻲ ﮔﺎﻫﻲ ﺍﺷﺘﺒﺎﻫﻲ ﻫﻢ ﺭﺥ ﻣﻲﺩﻫـﺪ‬

‫ﻛﻪ ﺍﻳﻦ ﺍﺷﺘﺒﺎﻩ ﺍﺻﻼﺡ ﻣﻲﺷﻮﺩ ﻭ ﺑﻪ ﺁﻥ ‪ Proof reading‬ﻣﻲﮔﻮﻳﻨﺪ‪ .‬ﻭﻇﻴﻔﻪ ﺍﺻﻠﻲ ﺍﺻﻼﺡ ‪ DNA‬ﺑﻪ ﻋﻬﺪﻩ ﺯﻳﺮﻭﺍﺣﺪ ‪ε‬‬

‫ﺁﻧﺰﻳﻢ ‪ DNA‬ﭘﻠﻲﻣﺮﺍﺯ ‪ III‬ﺑﺎ ﺧﺎﺻﻴﺖ ﺍﮔﺰﻭﻧﻮﻛﻠﺌﺎﺯﻱ ‪ 3′ → 5′‬ﺍﺳﺖ ﻛﻪ ﺑﺎﺯ ﺍﺷﺘﺒﺎﻩ ﺭﺍ ﺧﺎﺭﺝ ﻣﻲﻛﻨﺪ ﻭ ﺑﺎﺯ ﺻـﺤﻴﺢ ﺩﺭ‬

‫ﺟﺎﻱ ﺁﻥ ﻗﺮﺍﺭ ﻣﻲﺩﻫﺪ‪ .‬ﻋﻤﻞ ﺍﺻﻼﺡ ‪ DNA‬ﻧﻴﺰ ﮔﺎﻫﻲ ﺩﭼﺎﺭ ﺍﺷﺘﺒﺎﻩ ﻣﻲﺷﻮﺩ ﻛﻪ ﻣﻴﺰﺍﻥ ﺍﻳﻦ ﺍﺷﺘﺒﺎﻩ ‪ 10−3‬ﺗﻌﻴﻴﻦ ﺷـﺪﻩ‬

‫ﺍﺳــﺖ ﻭ ﭼــﻮﻥ ﻋﻤــﻞ ﻫﻤﺎﻧﻨﺪﺳــﺎﺯﻱ ﻧﻴــﺰ ﺑــﻪ ﻣﻴــﺰﺍﻥ ‪ 10−4‬ﺩﭼــﺎﺭ ﺍﺷــﺘﺒﺎﻩ ﻣــﻲﺷــﻮﺩ ﺩﺭ ﻣﺠﻤــﻮﻉ ﺑﺮﺁﻳﻨــﺪ ﺍﻳــﻦ ﺩﻭ‬
‫ﺍﺷﺘﺒﺎﻩ ‪ 10−4 ×10−3 = 10−7‬ﺧﻮﺍﻫﺪ ﺑﻮﺩ ﻭ ﭼﻮﻥ ﮊﻧﻮﻡ ﺑﺎﻛﺘﺮﻱ ‪ E.coli‬ﺑﺮﺍﺑﺮ ﺑـﺎ ‪ 5 ×106‬ﺍﺳـﺖ ﭘـﺲ ﺩﺭ ﻫـﺮ ﺑـﺎﺭ‬

‫ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﺗﻘﺮﻳﺒ ﹰﺎ ﻓﻘﻂ ﻳﻚ ﻧﻮﻛﻠﺌﻮﺗﻴﺪ ﺍﺯ ﮊﻧﻮﻡ ‪ E.coli‬ﺗﻐﻴﻴﺮ ﻣـﻲﻛﻨـﺪ ﻭ ﺍﻳـﻦ ﻧـﺸﺎﻥﺩﻫﻨـﺪﻩ ﺩﻗـﺖ ﺑـﺴﻴﺎﺭ ﺑـﺎﻻﻱ‬

‫ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﺍﺳﺖ‪ .‬ﻫﻤﭽﻨﻴﻦ ﺩﺭ ﻫﻨﮕﺎﻡ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ‪ RNA‬ﺁﻏﺎﺯﮔﺮ ﻗﻄﻌﺎﺕ ﺍﻭﻛـﺎﺯﺍﻛﻲ ﺭﺷـﺘﻪ ﺗـﺎﺧﻴﺮ ﺗﻮﺳـﻂ ‪DNA‬‬

‫ﭘﻠﻲﻣﺮﺍﺯ ‪ I‬ﻳﺎ ‪ R N ase H‬ﺧﺎﺭﺝ ﻣﻲﺷﻮﻧﺪ ﻭ ﺳﭙﺲ ﺁﻧﺰﻳﻢ ‪ DNA‬ﭘﻠﻲﻣﺮﺍﺯ ‪ I‬ﻓﻮﺍﺻﻞ ﺧﺎﻟﻲ ﺍﻳﺠﺎﺩ ﺷﺪﻩ ﺭﺍ ﭘﺮ ﻣﻲﻛﻨﺪ ﻭ‬

‫‪ DNA‬ﻟﻴﮕﺎﺯ ﺑﺎ ﺍﺳﺘﻔﺎﺩﻩ ﺍﺯ ﻛﻤﻚ ﮔﻬﺮﻣﺎﻳﻪ ‪ NAD +‬ﺩﺭ ﭘﺮﻭﻛﺎﺭﻳﻮﺗﻬﺎ ﻳﺎ ‪ ATP‬ﺩﺭ ﻳﻮﻛﺎﺭﻳﻮﺗﻬﺎ ﻗﻄﻌﺎﺕ ﺭﺍ ﺑﻪ ﻫﻢ ﻣﺘﺼﻞ‬

‫ﻣﻲﻛﻨﺪ‪ .‬ﭘﺲ ﺍﺯ ﺗﻜﻤﻴﻞ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ‪ ،‬ﻣﺮﺣﻠﻪ ﭘﺎﻳﺎﻥ ﻳﺎ ﺧﺎﺗﻤﻪ ﺍﺳﺖ‪ .‬ﭘﺎﻳﺎﻥ ﻫﻤﺎﻧﻨﺪﺳـﺎﺯﻱ ﺑـﺎﻛﺘﺮﻱ ‪ E.coli‬ﺩﺭ ﻣﻨﻄﻘـﻪ‬

‫ﻭﺳﻴﻊ ‪ ٣٥٠ kb‬ﻛﻪ ﺷﺎﻣﻞ ﻫﻔﺖ ﺟﺎﻳﮕﺎﻩ ﭘﺎﻟﻴﻨﺪﺭﻭﻣﻲ ‪ ٢٣‬ﺟﻔﺖﺑﺎﺯﻱ ﻣﻮﺳﻮﻡ ﺑﻪ ﺟﺎﻳﮕﺎﻫﻬـﺎﻱ ﭘﺎﻳـﺎﻥ ) ‪Termination‬‬

‫‪ (Sites‬ﺍﻧﺠﺎﻡ ﻣﻲﮔﻴﺮﺩ‪ .‬ﺟﺎﻳﮕﺎﻩ ﭘﺎﻳﺎﻥ ﺩﺭ ﻧﻘﻄﻪ ﻣﻘﺎﺑﻞ ﺟﺎﻳﮕﺎﻩ ﺷﺮﻭﻉ ) ‪ ( Oric‬ﻗﺮﺍﺭ ﺩﺍﺭﺩ‪ .‬ﺩﻭ ﭼﻨﮕﺎﻝ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﻛﻪ ﺍﺯ‬

‫ﻣﺒﺪﺃ ﺷﺮﻭﻉ ﻣﻲﺷﻮﺩ ﻭ ﺩﺭ ﺩﻭ ﺟﻬﺖ ﻣﺨﺎﻟﻒ ﻫﻤﺪﻳﮕﺮ ﺣﺮﻛﺖ ﻣـﻲﻛﻨﻨـﺪ‪ .‬ﭼﻨﮕـﺎﻝ ﻫﻤﺎﻧﻨﺪﺳـﺎﺯﻱ ﻛـﻪ ﺩﺭ ﺟﻬـﺖ ﺧـﻼﻑ‬

‫ﻋﻘﺮﺑﻪﻫﺎﻱ ﺳﺎﻋﺖ ﺣﺮﻛﺖ ﻣﻲﻛﻨﺪ ﺍﺯ ﺟﺎﻳﮕﺎﻫﻬﺎﻱ ﭘﺎﻳﺎﻥ ‪ B ، F ، G‬ﻭ ‪ C‬ﻋﺒﻮﺭ ﻣﻲﻛﻨﺪ ﻭ ﺩﺭ ﺟﺎﻳﮕﺎﻫﻬﺎﻱ ﭘﺎﻳﺎﻥ ‪ D ، A‬ﻳﺎ‬

‫‪ E‬ﻣﺘﻮﻗﻒ ﻣﻲﮔﺮﺩﺩ‪ .‬ﺍﺯ ﻃﺮﻓﻲ ﭼﻨﮕﺎﻝ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﻛﻪ ﺩﺭ ﺟﻬﺖ ﻋﻘﺮﺑﻪﻫﺎﻱ ﺳﺎﻋﺖ ﺣﺮﻛﺖ ﻣﻲﻛﻨﺪ ﺍﺯ ﺟﺎﻳﮕﺎﻫﻬـﺎﻱ ‪، E‬‬

‫‪ D‬ﻭ ‪ A‬ﻋﺒﻮﺭ ﻛﺮﺩﻩ ﻭ ﺩﺭ ‪ F ، B ، C‬ﻳﺎ ‪ G‬ﻣﺘﻮﻗﻒ ﻣﻲﮔﺮﺩﺩ‪ .‬ﺟﺎﻳﮕﺎﻫﻬﺎﻱ ﭘﺎﻳﺎﻥ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﻗﻄﺒﻲ ) ‪ ( Polar‬ﻫﺴﺘﻨﺪ‬

‫ﺩﺭ ﭘﺎﻳﺎﻥ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﭘﺮﻭﺗﺌﻴﻨﻲ ﺑﻪ ﻧﺎﻡ ‪ Tus‬ﺷﺮﻛﺖ ﻣﻲﻛﻨﺪ ﻛﻪ ﻣﻮﻧﻮﻣﺮ ﺑﺎ ‪ ٣٠٩‬ﺍﺳﻴﺪ ﺁﻣﻴﻨﻪ ﺍﺳﺖ ﻛﻪ ﺑﻪ ﺟﺎﻳﮕﺎﻩ ﭘﺎﻳﺎﻥ‬

‫ﻣﺘﺼﻞ ﻣﻲﺷﻮﺩ ﺍﺯ ﺑﺎﺯ ﺷﺪﻥ ﺩﻭ ﺭﺷﺘﻪ ‪ DNA‬ﺗﻮﺳﻂ ﻫﻠﻴﻜﺎﺯ ‪ dnaB‬ﺟﻠﻮﮔﻴﺮﻱ ﻣﻲﻛﻨﺪ‪ .‬ﭘﺮﻭﺗﺌﻴﻦ ‪ Tus‬ﺗﻨﻬﺎ ﻣﻲﺗﻮﺍﻧـﺪ‬

‫ﭼﻨﮕﺎﻝ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﺭﺍ ﺩﺭ ﻳﻚ ﺟﻬﺖ ﻣﺘﻮﻗﻒ ﻛﻨﺪ‪ .‬ﺩﺭ ﭘﺎﻳﺎﻥ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﺩﻭ ﻛﺮﻭﻣﻮﺯﻭﻡ ﺣﻠﻘﻮﻱ ﺍﻳﺠﺎﺩ ﻣﻲﺷﻮﺩ ﻛـﻪ ﺩﺭ‬

‫ﻗﺴﻤﺘﻲ ﺑﻪ ﻫﻢ ﻣﺘﺼﻞ ﻫﺴﺘﻨﺪ ﻛﻪ ﺑﻪ ﺁﻥ ﻛﺎﺗﻨﺎﻥ ) ‪ ( Catenane‬ﮔﻔﺘﻪ ﻣﻲﺷﻮﺩ‪ .‬ﺳﭙﺲ ﺑﻪ ﻭﺳﻴﻠﻪ ﻓﻌﺎﻟﻴـﺖ ﺩﻛﺎﺗﻨﺎﺳـﻴﻮﻥ‬

‫) ‪ ( Decatenation‬ﻧﻮﻋﻲ ﺁﻧﺰﻳﻢ ﺗﻮﭘﻮﺍﻳﺰﻭﻣﺮﺍﺯ ‪ II‬ﺑﻪ ﻧﺎﻡ ﺗﻮﭘﻮﺍﻳﺰﻭﻣﺮﺍﺯ ‪ IV‬ﺍﺯ ﻳﻜﺪﻳﮕﺮ ﺟﺪﺍ ﻣﻲﺷﻮﻧﺪ‪.‬‬

‫‪ -‬ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﺑﻪ ﺭﻭﺵ ﺩﺍﻳﺮﻩ ﻏﻠﺘﺎﻥ‪ :‬ﻧﻮﻉ ﺩﻳﮕﺮﻱ ﺍﺯ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﺩﺭ ﭘﺮﻭﻛﺎﺭﻳﻮﺗﻬﺎ ﻣﻲﺑﺎﺷﺪ ﻛﻪ ﺩﺭ ﺗﻜﺜﻴﺮ ﺑﻌﻀﻲ ﺍﺯ ﻓﺎﮊﻫﺎ‬

‫ﻭ ﭘﻼﺳﻤﻴﺪﻫﺎ‪ ،‬ﻓﺎﻛﺘﻮﺭ ﺟﻨﺴﻲ ‪ ، F‬ﺑﺎﻛﺘﺮﻱﻫﺎ‪ ،‬ﺗﺰﺍﻳﺪ ﮊﻧﻲ ﺩﻳﺪﻩ ﻣﻲﺷﻮﺩ‪ .‬ﺍﺑﺘﺪﺍ ﺩﺭ ﻧﺎﺣﻴﻪ ﺧﺎﺹ ﻳﻜﻲ ﺍﺯ ﺭﺷﺘﻪﻫـﺎﻱ ‪DNA‬‬
‫ﺣﻠﻘﻮﻱ ﺑﺮﻳﺪﻩ ﻣﻲﺷﻮﺩ‪ ،‬ﺳﭙﺲ ‪ 5′‬ﺍﻧﺘﻬﺎﻳﻲ ﺭﺷﺘﻪ ﺑﺮﻳﺪﻩ ﺷﺪﻩ ﺁﺯﺍﺩ ﺑﺎﻗﻲ ﻣﻲﻣﺎﻧﺪ‪ ،‬ﺩﺭ ﺣـﺎﻟﻲ ﻛـﻪ ﺍﻧﺘﻬـﺎﻱ ‪ 3′ − OH‬ﺑـﻪ‬

‫ﻋﻨﻮﺍﻥ ﻣﺤﻞ ﺍﺿﺎﻓﻪ ﺷﺪﻩ ﻧﻮﻛﻠﺌﻮﺗﻴﺪﻫﺎ ﺩﺭ ﺍﺧﺘﻴﺎﺭ ﺁﻧﺰﻳﻢ ‪ DNA‬ﭘﻠﻲﻣﺮﺍﺯ ‪ III‬ﻗﺮﺍﺭ ﻣﻲﮔﻴﺮﺩ‪ .‬ﺍﻳﻦ ﺁﻧﺰﻳﻢ ﺷـﺮﻭﻉ ﺑـﻪ ﻋﻤـﻞ‬

‫ﻣﻲﻛﻨﺪ ﻭ ﺑﻪ ﺗﺪﺭﻳﺞ ﻣﻜﻤﻞ ﺭﺷﺘﻪ ﺩﺍﺧﻠﻲ ﺭﺍ ﻣﻲﺳﺎﺯﺩ‪ .‬ﺍﻳﻦ ﻛﺎﺭ ﺑﺎ ﺣﺮﻛﺖ ﻛﺮﺩﻥ ﺁﻧﺰﻳﻢ ‪ DNA‬ﭘﻠﻲﻣﺮﺍﺯ ‪ III‬ﻭ ﭘﺮﻭﺗﺌﻴﻨﻬﺎﻱ‬

‫ﻫﻤﺮﺍﻩ ﺁﻥ ﺍﺩﺍﻣﻪ ﻣﻲﻳﺎﺑﺪ ﻭ ﺭﺷﺘﻪ ﺭﺍﻫﻨﻤﺎ ﺩﺭ ﺟﻬﺖ ‪ 5′‬ﺑﻪ ‪ 3′‬ﺳﺎﺧﺘﻪ ﻣﻲﺷﻮﺩ‪.‬‬

‫‪ -‬ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﭘﻼﺳﻤﻴﺪ‪ :‬ﭘﻼﺳﻤﻴﺪ‪ ،‬ﻗﻄﻌﺎﺕ ‪ DNA‬ﺣﻠﻘﻮﻱ ﻫـﺴﺘﻨﺪ ﻛـﻪ ﺩﺭ ﺩﺍﺧـﻞ ﺳﻴﺘﻮﭘﻼﺳـﻢ ﺑﺎﻛﺘﺮﻳﻬـﺎ ﻭ ﺟـﺪﺍ ﺍﺯ‬

‫ﻛﺮﻭﻣﻮﺯﻭﻡ ﺁﻧﻬﺎ ﻗﺮﺍﺭ ﺩﺍﺭﻧﺪ ﻭ ﺑﻪ ﻃﻮﺭ ﻣﺴﺘﻘﻞ ﺗﻜﺜﻴـﺮ ﭘﻴـﺪﺍ ﻣـﻲﻛﻨﻨـﺪ ﻭ ﺧـﺼﻮﺻﻴﺎﺕ ﺑـﺴﻴﺎﺭ ﻣﻬﻤـﻲ ﺩﺭ ﺧﻨﺜـﻲ ﻧﻤـﻮﺩﻥ‬

‫ﺁﻧﺘﻲﺑﻴﻮﺗﻴﻜﻬﺎ ﻭ ﻛﺎﺭﺑﺮﺩ ﺁﻧﻬﺎ ﺩﺭ ﻣﻬﻨﺪﺳﻲ ﮊﻧﺘﻴﻜﻲ ﺩﺍﺭﻧﺪ‪ .‬ﻋﻤﻞ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﭘﻼﺳﻤﻴﺪ ﺑﻪ ﺻﻮﺭﺕ ﺧﺎﺻﻲ ﺍﻧﺠﺎﻡ ﻣﻲﮔﻴﺮﺩ‪.‬‬

‫ﺁﻧﺰﻳﻢ ﻭﺍﺳﺮﺷﺘﻪ ﻛﺮﺩﻥ ‪ DNA‬ﺭﺍ ﺩﺭ ﺩﺭﻭﻥ ﺧﻮﺩ ﺍﻧﺠﺎﻡ ﻣﻲﺩﻫﺪ‪ .‬ﺩﺭ ﺍﺑﺘﺪﺍﻱ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﭘﻼﺳﻤﻴﺪ ‪ RNA‬ﺍﻱ ﺑﻪ ﻭﺟـﻮﺩ‬

‫ﻣﻲﺁﻳﺪ ﻛﻪ ﺣﺎﻟﺖ ﭼﻨﺪﺣﻠﻘﻪﺍﻱ ﻳﺎ ﻣﻮﻟﺘﻲﻟﻮﭖ ) ‪ ( Multiloop‬ﺩﺍﺭﺩ ﻛﻪ ﺑـﻪ ‪ DNA‬ﺗـﻚﺭﺷـﺘﻪﺍﻱ ﻣﺘـﺼﻞ ﺷـﺪﻩ‪ ،‬ﻣﺎﻧﻨـﺪ‬

‫ﭘﺮﻭﺗﺌﻴﻦ ‪ SSB‬ﺩﺭ ﺑﺎﻛﺘﺮﻱ ﻋﻤﻞ ﻣﻲﻛﻨﺪ ﻭ ﻣﺎﻧﻊ ﺍﺯ ﺍﺗﺼﺎﻝ ﺩﻭ ﺭﺷﺘﻪ ‪ DNA‬ﺩﺭ ﻫﻨﮕﺎﻡ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﻣـﻲﺷـﻮﺩ‪ .‬ﺁﻧـﺰﻳﻢ‬

‫ﻣﺴﺌﻮﻝ ﭘﻠﻲﻣﺮﻳﺰﺍﺳﻴﻮﻥ ﻭ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﭘﻼﺳﻤﻴﺪ ‪ DNA‬ﭘﻠﻲﻣﺮﺍﺯ ‪ I‬ﺍﺳﺖ ﻛﻪ ﺩﺭ ﺑﺎﻛﺘﺮﻱ ﻧﻘﺶ ﺗﺮﻣﻴﻢﻛﻨﻨﺪﻩ ﺩﺍﺭﺩ‪ .‬ﺑﺮﺍﻱ‬

‫ﺟﻠﻮﮔﻴﺮﻱ ﺍﺯ ﻫﻤﺰﻣﺎﻧﻲ ﻧﺴﺨﻪﺑﺮﺩﺍﺭﻱ ﻭ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ‪ ،‬ﭘﺮﻭﺗﺌﻴﻨﻲ ﺑﻪ ﻧﺎﻡ ‪ ROP‬ﻛﻪ ﺳﺮﻛﻮﺑﮕﺮ ‪Repressor of ) RNA‬‬

‫‪ (RNA‬ﻧﻴﺰ ﻧﺎﻣﻴﺪﻩ ﻣﻲﺷﻮﺩ‪ ،‬ﻭﺟﻮﺩ ﺩﺍﺭﺩ‪ .‬ﺍﻳﻦ ﭘﺮﻭﺗﺌﻴﻦ ﺗﺘﺮﺍﻣﺮ ﺑـﺎ ﺩﻭ ﻣـﺎﺭﭘﻴﭻ ﺁﻟﻔـﺎ ﻣﻴـﻞ ﺗﺮﻛﻴﺒـﻲ ﺷـﺪﻳﺪﻱ ﺑـﻪ ‪RNA‬‬

‫ﺩﺍﺭﺩ‪ R NA 2 , RNA1 .‬ﻣﻮﻟﺘﻲﻟﻮﭖ ﺭﺍ ﻛﻪ ﺑﺎﻋﺚ ﺑﺎﺯ ﺑﺎﻗﻴﻤﺎﻧﺪﻥ ﺩﻭ ﺭﺷﺘﻪ ‪ DNA‬ﺩﺭ ﻫﻨﮕﺎﻡ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﻣﻲﺷﻮﻧﺪ‪ ،‬ﺑـﻪ‬

‫ﻫﻢ ﻣﺘﺼﻞ ﻣﻲﻛﻨﺪ ﻭ ﻫﻴﺒﺮﻳﺪ ‪ RNA1, RNA 2‬ﺍﻳﺠﺎﺩ ﻣﻲﮔﺮﺩﺩ ﻭ ﺩﻭ ﺭﺷﺘﻪ ﻭﺍﺳﺮﺷﺘﻪ ﺷﺪﻩ ‪ DNA‬ﺩﻭﺑﺎﺭﻩ ﺑﻪ ﻳﻜـﺪﻳﮕﺮ‬

‫ﻣﺘﺼﻞ ﻣﻲﺷﻮﻧﺪ ﻭ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﺍﻧﺠﺎﻡ ﻧﻤﻲﮔﻴﺮﺩ‪.‬‬

‫‪ -‬ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﻭﻳﺮﻭﺳﻬﺎ‪ :‬ﻭﻳﺮﻭﺳﻬﺎ ﺑـﻪ ﺩﻭ ﺩﺳـﺘﻪ ﻭﻳﺮﻭﺳـﻬﺎﻱ ‪ DNA‬ﺩﺍﺭ ﻭ ﻭﻳﺮﻭﺳـﻬﺎﻱ ‪ RNA‬ﺩﺍﺭ ﺗﻘـﺴﻴﻢ ﻣـﻲﺷـﻮﻧﺪ‪.‬‬

‫ﻭﻳﺮﻭﺳﻬﺎﻱ ‪ DNA‬ﺩﺍﺭ ﺩﺭ ﺳﻪ ﮔﺮﻭﻩ ﻛﻠﻲ ﻗﺮﺍﺭ ﻣﻲﮔﻴﺮﻧﺪ‪:‬‬

‫‪ .۱‬ﻭﻳﺮﻭﺳﻬﺎﻱ ﺩﺍﺭﺍﻱ ‪ DNA‬ﺣﻠﻘﻮﻱ ﺗﻚﺭﺷﺘﻪﺍﻱ ﻣﺎﻧﻨﺪ ﻓﺎﮊ ‪ φ X 174‬ﻛﻪ ﻓﺮﻡ ﺗﻜﺜﻴﺮﺷﻮﻧﺪﻩ ﻳﺎ ‪Replication ) RF‬‬
 ‫‪ (Form‬ﺍﻳﺠﺎﺩ ﻣﻲﻛﻨﻨﺪ‪.‬‬

‫‪ .۲‬ﻭﻳﺮﻭﺳﻬﺎﻱ ﺩﺍﺭﺍﻱ ‪ DNA‬ﺧﻄﻲ ﺩﻭ ﺭﺷﺘﻪﺍﻱ ﻣﺎﻧﻨﺪ ﺑﺎﻛﺘﺮﻳﻮﻓﺎﮊ ‪ ، λ‬ﻧﺴﺨﻪﻫﺎﻱ ﻣﺘﻌﺪﺩﻱ ﺍﺯ ﮊﻧﻮﻡ ﺑﻪ ﺻﻮﺭﺕ ﻣﺘﺼﻞ ﺑـﻪ‬

‫ﻫﻢ ﺍﻳﺠﺎﺩ ﻣﻲﺷﻮﻧﺪ ﻛﻪ ﺑﻪ ﺁﻥ ﻛﻨﻜﺎﺗﻤﺮ ) ‪ ( Concatmer‬ﻣﻲﮔﻮﻳﻨﺪ‪ ،‬ﺳﭙﺲ ﺁﻧﺰﻳﻢ ﻧﻮﻛﻠﺌﺎﺯ ﺁﻥ ﺭﺍ ﺟﺪﺍ ﻣﻲﻛﻨﺪ‪.‬‬

‫‪ .۳‬ﻭﻳﺮﻭﺳﻬﺎﻱ ﺩﺍﺭﺍﻱ ‪ DNA‬ﺣﻠﻘـﻮﻱ ﺩﻭﺭﺷـﺘﻪﺍﻱ ﻣﺎﻧﻨـﺪ ﻓـﺎﮊ ‪ PM S 2‬ﺩﺭ ﭘـﺴﻮﺩﻭﻣﻮﻧﺎﺱ‪ .‬ﻭﻳﺮﻭﺳـﻬﺎﻱ ‪ RNA‬ﺩﺍﺭ ﺑـﻪ‬

‫ﮔﺮﻭﻫﻬﺎﻱ ﻣﺨﺘﻠﻔﻲ ﺗﻘﺴﻴﻢ ﻣﻲﺷﻮﻧﺪ ﻛﻪ ﻫﻤﺎﻧﻨﺪﺳﺎﺯﻱ ﻫﺮ ﻛﺪﺍﻡ ﺧﺼﻮﺻﻴﺎﺕ ﺧﺎﺹ ﺧﻮﺩ ﺭﺍ ﺩﺍﺭﻧﺪ‪ RNA .‬ﺍﻳﻦ ﻭﻳﺮﻭﺳﻬﺎ ﺑﻪ‬

‫ﺻﻮﺭﺕ ‪ RNA‬ﻣﺜﺒﺖ ﻳﺎ ﻣﻨﻔﻲ ﻣﻲﺑﺎﺷﺪ‪ RNA .‬ﻣﺜﺒﺖ‪ RNA ،‬ﺍﻱ ﺍﺳﺖ ﻛﻪ ﺑﻪ ﻃﻮﺭ ﻣﺴﺘﻘﻴﻢ ﺑﺮﺍﻱ ﺳﺎﺧﺖ ﭘﺮﻭﺗﺌﻴﻦ ﻣﻮﺭﺩ‬

‫ﺍﺳﺘﻔﺎﺩﻩ ﻗﺮﺍﺭ ﻣﻲﮔﻴﺮﺩ ﻭﻟﻲ ‪ RNA‬ﻣﻨﻔﻲ ﻧﻤﻲﺗﻮﺍﻧﺪ ﺑﻪ ﻋﻨﻮﺍﻥ ﺍﻟﮕﻮﻱ ﭘﺮﻭﺗﺌﻴﻦﺳﺎﺯﻱ ﻋﻤﻞ ﻛﻨﺪ ﻭ ﺑﺎﻳﺪ ﺍﺑﺘﺪﺍ ‪ RNA‬ﻣﻜﻤﻞ‬

‫ﺁﻥ ﺳﺎﺧﺘﻪ ﺷﻮﺩ‪ .‬ﮊﻧﻮﻡ ﺍﻳﻦ ﻭﻳﺮﻭﺳﻬﺎ ﺩﺭ ﺩﺍﺧﻞ ﺳﻠﻮﻝ ﻣﻴﺰﺑﺎﻥ ﺑﻪ ﺩﻭ ﺣﺎﻟﺖ ﻳﺎﻓﺖ ﻣﻲﺷﻮﺩ‪:‬‬

‫‪ RNA .۱‬ﺩﻭﺭﺷﺘﻪﺍﻱ ﻣﺘﺼﻞ ﺑﻪ ﻫـﻢ ﻛـﻪ ﻣﻜـﺮﺭ ﺍﺯ ﺁﻥ ﻧـﺴﺨﻪﺑـﺮﺩﺍﺭﻱ ﻣـﻲﺷـﻮﺩ ﻭ ﺑـﻪ ﺁﻥ ﻓـﺮﻡ ﺗﻜﺜﻴﺮﺷـﻮﻧﺪﻩ ﻳـﺎ ‪RF‬‬

‫) ‪ ( Replication Form‬ﻣﻲﮔﻮﻳﻨﺪ‪.‬‬

‫‪ .۲‬ﻫﻨﮕــﺎﻣﻲ ﻛــﻪ ﺍﺯ ﺭﻭﻱ ‪ RF‬ﺗﻜﺜﻴــﺮ ﺻــﻮﺭﺕ ﻣــﻲﮔﻴــﺮﺩ ﺑــﻪ ﺁﻥ ﻭﺍﺳــﻂ ﺗﻜﺜﻴﺮﺷــﻮﻧﺪﻩ ﻳــﺎ ‪Replication ) RI‬‬

‫ﻼ ﻣﻘﺎﻭﻡ ﺍﺳﺖ ﻭﻟﻲ ﻓﺮﻡ ‪ RI‬ﺑﻪ ﻃﻮﺭ‬

‫‪ (Intermediate‬ﮔﻔﺘﻪ ﻣﻲﺷﻮﺩ‪ .‬ﺷﻜﻞ ‪ RF‬ﻧﺴﺒﺖ ﺑﻪ ﺁﻧﺰﻳﻢ ‪ RNAase H‬ﻛﺎﻣ ﹰ‬

‫ﻧﺴﺒﻲ ﻣﻘﺎﻭﻡ ﺍﺳﺖ‪ .‬ﺩﺭ ﺩﺍﺧﻞ ﺳﻠﻮﻝ ﺍﺑﺘﺪﺍ ﺷﻜﻞ ‪ RF‬ﺍﻳﺠﺎﺩ ﻣﻲﺷﻮﺩ‪ ،‬ﺑﻪ ﺍﻳﻦ ﺻﻮﺭﺕ ﻛﻪ ﺭﺷﺘﻪ ﻣﻜﻤﻞ ﺭﺷﺘﻪ ‪ RNA‬ﻣﺜﺒﺖ‬

‫ﮊﻧﻮﻡ ﻓﺎﮊ ﺳﺎﺧﺘﻪ ﻣﻲﺷﻮﺩ‪ ،‬ﺳﭙﺲ ﺍﻳﻦ ﺭﺷﺘﻪ ﻣﻜﻤﻞ ﻛﻪ ﻣﻨﻔﻲ ﺍﺳﺖ ﺑﻪ ﻋﻨﻮﺍﻥ ﻭﺍﺳﻂ ﺗﻜﺜﻴﺮﺷﻮﻧﺪﻩ ﻳﺎ ‪ RI‬ﻋﻤـﻞ ﻛـﺮﺩﻩ ﻭ‬

‫ﺷﺮﻭﻉ ﺑﻪ ﺳﺎﺧﺘﻦ ‪ RNA‬ﻣﺜﺒﺖ ﻣﻲﻛﻨﺪ ﻭ ﺑﻪ ﺍﻳﻦ ﺻﻮﺭﺕ ﻓﺎﮊ ﺗﻜﺜﻴﺮ ﻣﻲﺷﻮﺩ‪.‬‬