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13.6:

์ง„ํ•ต์ƒ๋ฌผ์—์„œ์˜ ๋ณต์ œ

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Replication in Eukaryotes

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– [๊ฐ•์‚ฌ] ๋ณต์ œ ์‹œ ์‚ฌ์šฉ๋˜๋Š” ๋Œ€๋ถ€๋ถ„์˜ ์›ํ•ต์„ฑ ์ธ์ž๋Š”์ง„ํ•ต์„ฑ DNA ๋ณต์ œ์— ๋Œ€ํ•ด์„œ๋„๋น„์Šทํ•œ ์—ญํ• ์„ ํ•ฉ๋‹ˆ๋‹ค์ด ๋ณต์ œ ํ”„๋กœ์„ธ์Šค๋Š” ์ธ์‹ ์ฝคํ”Œ๋ ‰์Šค(ORC)๊ฐ€ ๊ฒฐํ•ฉ๋˜๋Š”๋ณต์ œ ์›์ ์—์„œ ์‹œ์ž‘๋ฉ๋‹ˆ๋‹ค๊ทธ๋Ÿฐ ๋‹ค์Œ ๋‚˜์„ ํšจ์†Œ๊ฐ€ ์œ ์ธ๋˜์–ด(๋Œ๋ ค ์™€์„œ)DNA ๊ฐ€๋‹ฅ์„ ํ’€์–ด๋‚ด๊ณ ๋‘ ๊ฐœ์˜ ๋ณต์ œ ๋ถ„๊ธฐ์ ์œผ๋กœ ๊ธฐํฌ๋ฅผ ๋งŒ๋“ค์–ด๋ƒ…๋‹ˆ๋‹ค๋˜ํ•œ ํ”„๋ฆฌ๋งˆ์ œ๋„ ๋„์ฐฉํ•ด์„œ RNA ํ”„๋ผ์ด๋จธ๋ฅผ ํ•ฉ์„ฑํ•˜๋Š”๋ฐ์ด๊ฒƒ์€ ๋‚˜์„ ํšจ์†Œ๊ฐ€ ์›€์ง์ด๋ฉด์„œDNA ์ค‘ํ•ฉํšจ์†Œ๊ฐ€ ์ƒˆ๋กœ์šด DNA๋กœ ์—ฐ์žฅ๋˜๋Š” ๊ฒƒ์ž…๋‹ˆ๋‹ค์›ํ•ต ์ƒ๋ฌผ์—์„œ์™€ ๊ฐ™์ด, ์ƒˆ๋กญ๊ฒŒ ํ˜•์„ฑ๋œ ์•ž์„œ๋Š” ๊ฐ€๋‹ฅ์€๊ณ„์†ํ•ด์„œ ์„ฑ์žฅํ•˜๋ฉฐ, ๋ฐ˜๋Œ€๋กœ ๋’ค์ฒ˜์ง€๋Š” ๊ฐ€๋‹ฅ์€ ๋ณต์ œ ๋ถ„๊ธฐ์ ์„ ๋”ฐ๋ผ์ž‘์€ ์˜ค์นด์žํ‚ค ๋ถ„์ ˆ๋กœ ์ƒ์„ฑ๋˜์–ด๋ถ„๊ธฐ์ ๊ณผ ๋ฐ˜๋Œ€ ๋ฐฉํ–ฅ์œผ๋กœ ์ด๋™ํ•ฉ๋‹ˆ๋‹ค์—ฌ๋Ÿฌ ์š”์ธ๋“ค ๋•Œ๋ฌธ์—, ์ด ๊ตฌ์กฐ์˜ ์ ˆ๋ฐ˜์—์„œ์•ž์„œ๋Š” ๊ฐ€๋‹ฅ์„ ์ƒ์„ฑํ•˜๋Š”๋ฐ ์‚ฌ์šฉ๋˜๋Š” DNA ์ฃผํ˜•์ด๋‹ค๋ฅธ ์ ˆ๋ฐ˜์—์„œ๋Š” ๋’ค์ฒ˜์ง€๋Š” ๊ฐ€๋‹ฅ์„ ์ƒ์„ฑํ•ฉ๋‹ˆ๋‹คํฅ๋ฏธ๋กญ๊ฒŒ๋„, ๋‹ค์–‘ํ•œ ๋ณต์ œ ๊ธฐ์ ์€์„ ํ˜• ์ง„ํ•ต ์—ผ์ƒ‰์ฒด์— ์กด์žฌํ•˜๋ฉฐ๋ณต์ œ๋Š” ์—ฐ๊ด€๋œ ๊ตฌ๊ฐ€ ๊ฒฐํ•ฉ๋  ๋•Œ ์ข…๋ฃŒ๋ฉ๋‹ˆ๋‹ค๊ทธ๋Ÿฌ๊ณ  ๋‚˜์„œ ํ”„๋ผ์ด๋จธ๋Š” RNAse์™€ ๊ฐ™์€ ํšจ์†Œ๋ฅผ ํ†ตํ•ด ์ œ๊ฑฐ๋˜๊ณ DNA์šฉ์œผ๋กœ ์ฑ„์ทจ๋ฉ๋‹ˆ๋‹ค์ดํ›„ DNA ๋ฆฌ๊ฐ€์•„์ œ๋Š” ๋ชจ๋“  ์„ธ๊ทธ๋จผํŠธ์— ๋ถ€์ฐฉํ•ฉ๋‹ˆ๋‹คํ•˜์ง€๋งŒ ์—”๋“œ ํ”„๋ผ์ด๋จธ๊ฐ€ ๋’ค์ฒ˜์ง€๋Š” ๊ฐ€๋‹ฅ์—์„œ ์‚ฌ๋ผ์ง€๋ฉด๊ณต๊ฐ„์€์ด ๋น„์–ด ์žˆ๊ฒŒ ๋ฉ๋‹ˆ๋‹ค๊ทธ๋ฆฌ๊ณ  ๋ณต์‚ฌ๋˜์ง€ ์•Š์€ DNA ์ฃผํ˜•์ด ๊ทธ ์œ„์— ํŽผ์ณ์ ธ ์žˆ๊ฒŒ ๋ฉ๋‹ˆ๋‹ค์ด๊ฒƒ๊ณผ ์‹ธ์šฐ๊ธฐ ์œ„ํ•ด, ํ…”๋กœ๋จธ๋ผ์•„์ œ๋ผ๊ณ  ๋ถˆ๋ฆฌ๋Š” ํšจ์†Œ๋Š”๊ณผ๋„ํ•˜๊ฒŒ ๋ป—์€ ๋ถ€์œ„์— ๋ถ™์–ด์ฝ”๋”ฉ๋˜์ง€ ์•Š์€ DNA ์—ผ๊ธฐ์„œ์—ด๋กœ ๊ทธ๊ฒƒ์„ ์—ฐ์žฅ์‹œํ‚ต๋‹ˆ๋‹คํ”„๋ฆฌ๋ฉ”์ด์ฆˆ ๋ฐ DNA ์ค‘ํ•ฉํšจ์†Œ๋Š” ์ด ํ™•์žฅ๋œ ์˜์—ญ์— ์ž‘์šฉํ•˜์—ฌ๋‹ค์ค‘ ๋ณต์ œ ๋„์ค‘์— ๋’ค์ฒ˜์ง€๋Š” ๊ฐ€๋‹ฅ์—์„œDNA ์ฝ”๋”ฉ ์†์‹ค์„ ๋ณดํ˜ธํ•˜๋Š” ํ…”๋กœ๋ฏธ์–ด ์บก์„ ๋งŒ๋“ญ๋‹ˆ๋‹ค๋”ฐ๋ผ์„œ ์ง„ํ•ต DNA ๋ณต์ œ๋Š” ์–ด๋ฒ„์ด ๊ฐ€๋‹ฅ ๋ฐ์ƒˆ๋กœ ํ•ฉ์„ฑ๋œ ๊ฐ€๋‹ฅ์„ ๊ฐ€์ง„ ๋‘ ๊ฐœ์˜ DNA ๋ถ„์ž๋กœ๋‹ค์–‘ํ•œ ๋ณต์ œ ๊ธฐ์ ๊ณผ ํ…”๋กœ๋ฏธ์–ด๋กœ ๋๋‚ฉ๋‹ˆ๋‹ค

13.6:

์ง„ํ•ต์ƒ๋ฌผ์—์„œ์˜ ๋ณต์ œ

๊ฐœ์š”

์ง„ํ•ต์„ธํฌ(eukaryotic cell)์˜ DNA ๋ณต์ œ(replication)๋Š” ๊ณ ๋„๋กœ ๋ณด์กด๋˜๊ณ  ์—„๊ฒฉํ•˜๊ฒŒ ์กฐ์ ˆ๋ฉ๋‹ˆ๋‹ค. ์—ฌ๋Ÿฌ ๊ฐœ์˜ ์„ ํ˜•(linear) ์—ผ์ƒ‰์ฒด๋Š” ์„ธํฌ ๋ถ„์—ด ์ „์— ๋†’์€ ์ •ํ™•๋„(fidelity)๋กœ ๋ณต์ œ๋˜์–ด์•ผ ํ•˜๊ธฐ ๋•Œ๋ฌธ์— ๋ณต์ œ ๊ณผ์ •์—์„œ ์ „๋ฌธํ™”๋œ ์—ญํ• ์„ ํ•˜๋Š” ๋‹จ๋ฐฑ์งˆ์ด ๋งŽ์Šต๋‹ˆ๋‹ค. ๋ณต์ œ๋Š” ๊ฐœ์‹œ(initiation; ์‹œ์ž‘), ์—ฐ์žฅ(elongation; ์‹ ์žฅ), ์ข…๊ฒฐ(termination; ์ข…๋ฃŒ), ์ด๋ ‡๊ฒŒ ์„ธ ๋‹จ๊ณ„๋กœ ์ด๋ฃจ์–ด์ง€๋ฉฐ, ์ข…๊ฒฐ ํ›„์—” ํ•ต ์•ˆ์— ๋‘ ๊ฐœ์˜ ์™„์ „ํ•œ ์—ผ์ƒ‰์ฒด ์ง‘ํ•ฉ์ด ์žˆ๊ฒŒ ๋ฉ๋‹ˆ๋‹ค.

๋งŽ์€ ๋‹จ๋ฐฑ์งˆ์ด ๋ณต์ œ๊ธฐ์ ์—์„œ ๋ณต์ œ๋ฅผ ์กฐ์ •ํ•ฉ๋‹ˆ๋‹ค.

์ง„ํ•ต DNA ๋ณต์ œ๋Š” ์›ํ•ต DNA ๋ณต์ œ์™€ ๋™์ผํ•œ ์—ฌ๋Ÿฌ ์›๋ฆฌ๋“ค์„ ๋”ฐ๋ฅด์ง€๋งŒ, ์œ ์ „์ฒด๊ฐ€ ํ›จ์”ฌ ๋” ํฌ๊ณ  ์—ผ์ƒ‰์ฒด๊ฐ€ ์›ํ˜•์ด ์•„๋‹ˆ๋ผ ์„ ํ˜•์ด๊ธฐ ๋•Œ๋ฌธ์— ๋” ๋งŽ์€ ๋‹จ๋ฐฑ์งˆ์ด ํ•„์š”ํ•˜๋ฉฐ, ๋”ฐ๋ผ์„œ ๋ช‡ ๊ฐ€์ง€ ์ค‘์š”ํ•œ ์ฐจ์ด๋ฅผ ๋ณด์ž…๋‹ˆ๋‹ค. ๋ณต์ œ๋Š” ๊ฐ ์—ผ์ƒ‰์ฒด๋ฅผ ๋”ฐ๋ผ ์—ฌ๋Ÿฌ ๋ณต์ œ๊ธฐ์ (origin of replication; origin; ๋ณต์ œ์›์ )์—์„œ ๋™์‹œ์— ์ผ์–ด๋‚ฉ๋‹ˆ๋‹ค. ๊ฐœ์‹œ ๋‹จ๋ฐฑ์งˆ(initiator protein)์€ ๋ณต์ œ๊ธฐ์ ์„ ์ธ์‹ํ•ด ๊ฒฐํ•ฉํ•˜๊ณ , DNA ์ด์ค‘ ๋‚˜์„ ์„ ํ’€๊ธฐ ์œ„ํ•ด ๋‚˜์„ ํšจ์†Œ(helicase; ํ—ฌ๋ฆฌ์ผ€์ด์Šค)๋ฅผ ๋ชจ์ง‘ํ•ฉ๋‹ˆ๋‹ค. ๊ฐ ๋ณต์ œ๊ธฐ์ ์—์„œ 2๊ฐœ์˜ ๋ณต์ œ ๋ถ„๊ธฐ์ (replication fork; ๋ณต์ œ ํฌํฌ)์ด ํ˜•์„ฑ๋ฉ๋‹ˆ๋‹ค. ๊ทธ๋Ÿฐ ๋‹ค์Œ ํ”„๋ฆฌ๋ฉ”์ด์ฆˆ(primase; ํ”„๋ผ์ด๋ฉ”์ด์ฆˆ)๊ฐ€ DNA์˜ ๋‹จ์ผ ๊ฐ€๋‹ฅ์— ์งง์€ RNA ํ”„๋ผ์ด๋จธ(RNA primer; RNA ์‹œ๋ฐœ์ฒด)๋ฅผ ์ถ”๊ฐ€ํ•˜๋Š”๋ฐ, ์ด ํ”„๋ผ์ด๋จธ๋Š” DNA ์ค‘ํ•ฉํšจ์†Œ(DNA polymerase; DNA ํด๋ฆฌ๋จธ๋ ˆ์ด์Šค)๊ฐ€ ๊ฒฐํ•ฉํ•˜๊ณ  ์—ผ๊ธฐ์„œ์—ด์„ ๋ณต์ œํ•˜๊ธฐ ์‹œ์ž‘ํ•˜๋Š” ์ถœ๋ฐœ์  ์—ญํ• ์„ ํ•ฉ๋‹ˆ๋‹ค. DNA๋Š” 5’์—์„œ 3’ ๋ฐฉํ–ฅ์œผ๋กœ๋งŒ ํ•ฉ์„ฑ๋  ์ˆ˜ ์žˆ์œผ๋ฏ€๋กœ, ๋ณต์ œ๊ฐ€ ํ•œ ๋ณต์ œ ๋ถ„๊ธฐ์ ์˜ ์–‘์ชฝ ๊ฐ€๋‹ฅ์—์„œ ๋‘ ๋ฐฉํ–ฅ์œผ๋กœ ์ง„ํ–‰๋ฉ๋‹ˆ๋‹ค. ์„ ๋„๊ฐ€๋‹ฅ(leading strand; ์•ž์„œ๋Š” ๊ฐ€๋‹ฅ)์€ ์—ฐ์†ํ•ด์„œ ํ•ฉ์„ฑ๋˜๋Š” ๋ฐ˜๋ฉด, ์ง€์—ฐ๊ฐ€๋‹ฅ(lagging strand; ๋’ค์ณ์ง€๋Š” ๊ฐ€๋‹ฅ)์€ ๊ธธ์ด๊ฐ€ 100-200๊ฐœ์˜ ์—ผ๊ธฐ์Œ์œผ๋กœ ์งง๊ฒŒ ํ•ฉ์„ฑ๋˜๋Š”๋ฐ, ์ด๋ฅผ ์˜ค์นด์žํ‚ค ์ ˆํŽธ(Okazaki fragment; ์˜ค์นด์žํ‚ค ๋ถ„์ ˆ)์ด๋ผ๊ณ  ๋ถ€๋ฆ…๋‹ˆ๋‹ค. ๋ณต์ œ๊ฐ€ ๊ฑฐ์˜ ์™„๋ฃŒ๋˜๋ฉด RNase(ribonuclease; ๋ฆฌ๋ณดํ•ต์‚ฐ๊ฐ€์ˆ˜๋ถ„ํ•ดํšจ์†Œ) ํšจ์†Œ๊ฐ€ RNA ํ”„๋ผ์ด๋จธ๋ฅผ ์ œ๊ฑฐํ•˜๊ณ  DNA ์—ฐ๊ฒฐํšจ์†Œ(DNA ligase)๊ฐ€ ์ƒˆ๋กœ์šด ๊ฐ€๋‹ฅ์˜ ํ‹ˆ์„ ์ฑ„์›๋‹ˆ๋‹ค.

์ค‘ํ•ฉํšจ์†Œ ๊ฐ„ ๋ณต์ œ ์ž‘์—…์˜ ๋ถ„์—…

์ง„ํ•ต์ƒ๋ฌผ์˜ DNA๋ฅผ ๋ณต์ œํ•˜๋Š” ์ž‘์—…์€ ์—ฌ๋Ÿฌ ์ข…๋ฅ˜์˜ DNA ์ค‘ํ•ฉํšจ์†Œ ๊ฐ„ ๋ถ„์—…๋ฉ๋‹ˆ๋‹ค. ๋ชจ๋“  ์œ ๊ธฐ์ฒด์˜ DNA ์ค‘ํ•ฉํšจ์†Œ ๊ณ„์—ด์€ ๋‹จ๋ฐฑ์งˆ ๊ตฌ์กฐ์™€ ์•„๋ฏธ๋…ธ์‚ฐ ์„œ์—ด์˜ ์œ ์‚ฌ์„ฑ์— ๋”ฐ๋ผ ๋ถ„๋ฅ˜๋ฉ๋‹ˆ๋‹ค. ์ฒ˜์Œ ๋ฐœ๊ฒฌ๋œ ๊ณ„์—ด์€ A, B, C, X๋กœ ๋ถˆ๋ ธ๊ณ , Y, D ๊ณ„์—ด์€ ๋‚˜์ค‘์— ํ™•์ธ๋˜์—ˆ์Šต๋‹ˆ๋‹ค. ์ง„ํ•ต์ƒ๋ฌผ์˜ B ๊ณ„์—ด ์ค‘ํ•ฉํšจ์†Œ( Family B polymerase)๋Š” ๋ณต์ œ ๋ถ„๊ธฐ์ ์˜ ํ”„๋ฆฌ๋ฉ”์ด์ฆˆ ์—ญํ• ๋„ ํ•˜๋Š” Pol α์™€ DNA ๋ณต์ œ ์ž‘์—…์˜ ๋Œ€๋ถ€๋ถ„์„ ํ•˜๋Š” ํšจ์†Œ Pol δ์™€ Pol ε(๊ฐ๊ฐ ์ฃผํ˜•(template)์˜ ์ง€์—ฐ๊ฐ€๋‹ฅ๊ณผ ์„ ๋„๊ฐ€๋‹ฅ์—์„œ ์ž‘์—…)์„ ํฌํ•จํ•ฉ๋‹ˆ๋‹ค. ๋‹ค๋ฅธ DNA ์ค‘ํ•ฉํšจ์†Œ๋Š” DNA ์†์ƒ์„ ๋ณต๊ตฌํ•˜๊ณ , ๋ฏธํ† ์ฝ˜๋“œ๋ฆฌ์•„์™€ ์ƒ‰์†Œ์ฒด(plastid) DNA๋ฅผ ๋ณต์‚ฌํ•˜๊ณ , RNA ํ”„๋ผ์ด๋จธ๊ฐ€ ์ œ๊ฑฐ๋œ ํ›„ ์ง€์—ฐ๊ฐ€๋‹ฅ์˜ DNA ์„œ์—ด์˜ ํ‹ˆ์ƒˆ๋ฅผ ์ฑ„์šฐ๋Š” ๊ฒƒ๊ณผ ๊ฐ™์€ ์ž‘์—…์„ ๋‹ด๋‹นํ•ฉ๋‹ˆ๋‹ค.

ํ…”๋กœ๋ฏธ์–ด๋Š” ์—ผ์ƒ‰์ฒด์˜ ๋์„ ๋ถ„ํ•ด๋กœ๋ถ€ํ„ฐ ๋ณดํ˜ธํ•ฉ๋‹ˆ๋‹ค

์ง„ํ•ต์ƒ๋ฌผ ์—ผ์ƒ‰์ฒด๋Š” ์„ ํ˜•์ด๊ธฐ ๋•Œ๋ฌธ์— ๋๋ถ€๋ถ„์—์„œ ๋ถ„ํ•ด๋˜๊ธฐ ์‰ฝ์Šต๋‹ˆ๋‹ค. ์—ผ์ƒ‰์ฒด์˜ ๋์—๋Š” ์ค‘์š”ํ•œ ์œ ์ „ ์ •๋ณด๋ฅผ ์†์ƒ์œผ๋กœ๋ถ€ํ„ฐ ๋ณดํ˜ธํ•˜๊ธฐ ์œ„ํ•ด ํ…”๋กœ๋ฏธ์–ด(telomere; ๋ง๋‹จ์†Œ์ฒด)๊ฐ€ ์žˆ์Šต๋‹ˆ๋‹ค. ํ…”๋กœ๋ฏธ์–ด๋Š” ๋น„์•”ํ˜ธํ™”(non-coding; ๋น„๋ถ€ํ˜ธํ™”; ๋…ผ์ฝ”๋”ฉ)๋˜๊ณ  ๊ณ ๋„๋กœ ๋ณด์กด๋œ G-rich(์ฆ‰ ๊ตฌ์•„๋‹Œ(guanine)์ด ๋งŽ์€) ์„œ์—ด์ด ๋ฐ˜๋ณต๋œ DNA ๊ตฌ๊ฐ„์ž…๋‹ˆ๋‹ค. ์—ผ์ƒ‰์ฒด์˜ ์–‘์ชฝ ๋์— ์žˆ๋Š” ์งง์€ ๋‹จ์ผ ๊ฐ€๋‹ฅ 3’ ๋Œ์ถœ๋ถ€๋Š” ํ•ต ๋‚ด์—์„œ ์—ผ์ƒ‰์ฒด๋ฅผ ์•ˆ์ •์‹œํ‚ค๋Š” ํŠน์ˆ˜ ๋‹จ๋ฐฑ์งˆ๊ณผ ์ƒํ˜ธ์ž‘์šฉํ•ฉ๋‹ˆ๋‹ค. ๋งค ์„ธํฌ ๋ถ„ํ•  ์‹œ ํ…”๋กœ๋ฏธ์–ด ๊ตฌ๊ฐ„ ์ผ๋ถ€๋Š” ์ง€์—ฐ๊ฐ€๋‹ฅ์ด ํ•ฉ์„ฑ๋˜๋Š” ๋ฐฉ์‹ ๋•Œ๋ฌธ์— ๋ณต์ œ๋  ์ˆ˜ ์—†์Šต๋‹ˆ๋‹ค. ๊ทธ ๊ฒฐ๊ณผ, ํ…”๋กœ๋ฏธ์–ด๋Š” ์—ฌ๋Ÿฌ ์„ธํฌ ์ฃผ๊ธฐ๋ฅผ ๊ฑฐ์น˜๋ฉฐ ์ ์  ์งง์•„์ง€๊ณ , ๋”ฐ๋ผ์„œ ์„ธํฌ ๋…ธํ™”์˜ ์ง€ํ‘œ๋กœ ์ธก์ •๋  ์ˆ˜ ์žˆ์Šต๋‹ˆ๋‹ค. ์ƒ์‹์„ธํฌ(germ cell)์™€ ์ค„๊ธฐ์„ธํฌ(stem cell) ๊ฐ™์€ ํŠน์ • ์„ธํฌ๊ตฐ์€ ํ…”๋กœ๋ฏธ์–ด๋ฅผ ์—ฐ์žฅํ•˜๋Š” ํšจ์†Œ์ธ ํ…”๋กœ๋จธ๋ ˆ์ด์ฆˆ(telomerase; ํ…”๋กœ๋จธ๋ ˆ์ด์Šค)๋ฅผ ๋ฐœํ˜„ํ•˜์—ฌ ํ…”๋กœ๋ฏธ์–ด๊ฐ€ ์งง์•„์ง€๊ธฐ ์ „์— ์„ธํฌ๊ฐ€ ๋” ๋งŽ์€ ์„ธํฌ ์ฃผ๊ธฐ๋ฅผ ๊ฑฐ์น  ์ˆ˜ ์žˆ๋„๋ก ๋งŒ๋“ญ๋‹ˆ๋‹ค.

Suggested Reading

Garcia-Diaz, Miguel, and Katarzyna Bebenek. “Multiple functions of DNA polymerases.” Critical Reviews in Plant Sciences 26 (2007): 105-122. [Source]