What happens when your DNA is damaged? - Monica Menesini

譯者: Eunice Chang 審譯者: Max Chern

僅僅一個細胞中的DNA

The DNA in just one of your cells

gets damaged tens of thousands of times per day.

每一天就會發生數以萬次的損傷

Multiply that by your body's hundred trillion or so cells,

若再乘以身體內大概有百兆個細胞

and you've got a quintillion DNA errors everyday.

則每天有萬兆次(10的18次方) 的DNA錯誤會發生

And because DNA provides the blueprint

因為DNA提供了藍圖

for the proteins your cells need to function,

以製造蛋白質， 讓細胞能正常運作

damage causes serious problems, such as cancer.

DNA損害會造成嚴重的問題,像是癌症

The errors come in different forms.

DNA錯誤有許多不同型式

Sometimes nucleotides, DNA's building blocks, get damaged,

有時候是核苷酸 (DNA基本組成單位) 受到損壞

other times nucleotides get matched up incorrectly,

又有時候,核苷酸會配對錯誤

causing mutations,

造成突變

and nicks in one or both strands can interfere with DNA replication,

而DNA單股或雙股上有缺失時， 會阻礙它的複製

or even cause sections of DNA to get mixed up.

甚至會造成DNA的部分片段大亂

Fortunately, your cells have ways of fixing most of these problems

幸運的是，在大多數的時候

most of the time.

細胞有方法可以修復大部分的這些問題

These repair pathways all rely on specialized enzymes.

修復方法，主要依賴一些特殊酵素

Different ones respond to different types of damage.

不同的酵素處理不同的問題

One common error is base mismatches.

一個常見的錯誤是：鹼基配對錯誤

Each nucleotide contains a base,

每一個核苷酸有一個“鹼基”

and during DNA replication,

當ＤＮＡ複製的時候

the enzyme DNA polymerase is supposed to bring in the right partner

ＤＮＡ聚合酶會攜帶正確相對應的 “鹼基“

to pair with every base on each template strand.

來和在模板鏈上的每一個 “鹼基” 配對。

Adenine with thymine, and guanine with cytosine.

腺嘌呤會和胸腺嘧啶配對 尿嘧啶會和鳥嘌呤配對（A-T;C-G)

But about once every hundred thousand additions,

但是大約有十萬分之一的機率

it makes a mistake.

會發生錯誤

The enzyme catches most of these right away,

大半的錯誤，酵素會馬上查出

and cuts off a few nucleotides and replaces them with the correct ones.

然後切掉一些核苷酸， 並用正確的來取代

And just in case it missed a few,

為了以防萬一

a second set of proteins comes behind it to check.

第二組蛋白質會跟在後面檢查

If they find a mismatch,

如果他們發現配對錯誤

they cut out the incorrect nucleotide and replace it.

就會切掉錯誤的核苷酸 然後以正確的置換之

This is called mismatch repair.

稱為“錯配修復法“

Together, these two systems reduce the number of base mismatch errors

這兩個系統一起作用

to about one in one billion.

會將鹼基的配對錯誤機率降到十億萬分之一

But DNA can get damaged after replication, too.

但是DNA也可能會在複製後受損

Lots of different molecules can cause chemical changes to nucleotides.

很多不同的分子 會造成核苷酸產生化學變化

Some of these come from environmental exposure,

這些分子有的是來自環境的暴露

like certain compounds in tobacco smoke.

像香煙中含有的某些物質等

But others are molecules that are found in cells naturally,

但有些分子是細胞裡本來就有的

like hydrogen peroxide.

像是過氧化氫

Certain chemical changes are so common

這種化學變化很常見

that they have specific enzymes assigned to reverse the damage.

所以我們有一些特別的酵素 是專門負責來修復這些損傷

But the cell also has more general repair pathways.

不過，細胞也有更普通的修復方法

If just one base is damaged,

如果只有一個鹼基出現問題

it can usually be fixed by a process called base excision repair.

通常可用一種叫 “鹼基切除修復” 的方式來處理

One enzyme snips out the damaged base,

一個酵素剪掉受損的鹼基

and other enzymes come in to trim around the site and replace the nucleotides.

然後其他酵素就來幫忙修整受損的地方 並替換掉受損的核甘酸

UV light can cause damage that's a little harder to fix.

紫外線也可能造成損傷，而且會比較難修復

Sometimes, it causes two adjacent nucleotides to stick together,

有時，它會造成相鄰的核苷酸黏在一起

distorting the DNA's double helix shape.

使原本的DNA雙螺旋結構變形

Damage like this requires a more complex process

像這樣的損傷需要更複雜的步驟來修復

called nucleotide excision repair.

叫做“核苷酸切除修復法”

A team of proteins removes a long strand of 24 or so nucleotides,

一組蛋白質會移除一長串 大約24個左右的核苷酸

and replaces them with fresh ones.

然後用新的核苷酸來取代他們

Very high frequency radiation, like gamma rays and x-rays,

非常高頻的幅射， 像伽馬射線或是X-射線

cause a different kind of damage.

可造成ＤＮＡ不同種類的損傷

They can actually sever one or both strands of the DNA backbone.

他們可以造成DNA骨架的單股或雙股斷裂

Double strand breaks are the most dangerous.

“雙股斷裂”是最危險的

Even one can cause cell death.

甚至只是一處發生，也會造成細胞死亡

The two most common pathways for repairing double strand breaks

修復DNA雙股斷裂 最常見的兩個方法

are called homologous recombination and non-homologous end joining.

稱為 “同源重組” 和 “非同源末端接合”

Homologous recombination uses an undamaged section of similar DNA as a template.

同源重組是用一股 沒有受損且相似的DNA當作模板

Enzymes interlace the damaged and undamgaed strands,

酵素使被破壞的鏈與未受損的鏈交錯

get them to exchange sequences of nucleotides,

以交換核苷酸片段

and finally fill in the missing gaps

並填補缺損的間隙

to end up with two complete double-stranded segments.

最後就可以得到兩段完整的雙股DNA

Non-homologous end joining, on the other hand,

另一方面，非同源末端接合

doesn't rely on a template.

並不是用模板來修復

Instead, a series of proteins trims off a few nucleotides

而是需要一系列的蛋白質 來修剪掉一些核苷酸

and then fuses the broken ends back together.

然後使斷裂端融合在一起

This process isn't as accurate.

這個步驟並非總是那麼精確

It can cause genes to get mixed up, or moved around.

它可能會造成基因錯亂或是基因的易位

But it's useful when sister DNA isn't available.

但是當沒有相似複製DNA存在時，卻是很有用

Of course, changes to DNA aren't always bad.

當然，ＤＮＡ的改變並非都是不好的事

Beneficial mutations can allow a species to evolve.

有益的突變可以讓物種演化

But most of the time, we want DNA to stay the same.

但大多數的時候， 我們希望DNA可以維持不變

Defects in DNA repair are associated with premature aging

DNA修復有瑕疵與過早老化

and many kinds of cancer.

及許多癌症是有關的

So if you're looking for a fountain of youth,

所以如果你追求不老泉

it's already operating in your cells,

它早已存在每天運行不斷 億萬次修復的細胞中了

billions and billions of times a day.