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诺奖得主PNAS文章公布全新测序技术:重新定义DNA修复

2017-02-13 生物通 生物通

我们身体细胞内的DNA每日都会由于各种原因而受损,因此可以说细胞间DNA修复系统是维持生命的基础,但是对于这个基础机制科学家们并没有完全弄明白。近期来自北卡罗来纳州大学教堂山分校的研究人员利用先进的测序技术,分析澄清了这些修复系统中的关键分子细节,发现了核苷酸切除修复的奥秘。这一研究成果公布在2月6日的PNAS杂志上,文章的通讯作者之一是2015年诺贝尔化学奖得主之一Aziz Sancar教授,S


我们身体细胞内的DNA每日都会由于各种原因而受损,因此可以说细胞间DNA修复系统是维持生命的基础,但是对于这个基础机制科学家们并没有完全弄明白。近期来自北卡罗来纳州大学教堂山分校的研究人员利用先进的测序技术,分析澄清了这些修复系统中的关键分子细节,发现了核苷酸切除修复的奥秘。

这一研究成果公布在2月6日的PNAS杂志上,文章的通讯作者之一是2015年诺贝尔化学奖得主之一Aziz Sancar教授,Sancar教授生于土耳其萨武尔,主要从事DNA修复、细胞周期检查点、生物钟方面的研究。他获得诺贝尔奖的原因也就是DNA修复研究:他曾花费大量时间分析光解和光激活的机制,对这些机制的探索已有近20年时间,直接观察到了光解酶修复胸腺嘧啶二聚体的过程。

为了研究细胞中的切除修复,Sancar等人研发出了一种新技术:XR-seq,XR-seq能帮助研究人员分离和测序切除修复过程中从基因组剪切下来的小片段加合物损伤(adduct-damaged)DNA。了解俄这些DNA片段的序列,将有助于更精确的定位它们在基因组中的位置。

采用这种方法,研究人员于2015年首次构建出了人类基因组的UV修复图,并于2016年生成了抗癌顺铂药物对整个人类基因组的损伤和修复图谱。现在他们又利用XR-seq技术回答了关于大肠杆菌中损伤修复的一些基础性问题,这将有助于研发新型抗生素药物。

Mfd

在这项研究中,研究人员发现一种蛋白:Mfd在细菌的切除修复中扮演了独特的重要作用。

文章作者之一Christopher P. Selby博士表示,“我认为Mfd是大肠杆菌中最有趣的蛋白”。因为当一个细菌基因的DNA被转录成RNA,转录分子机制会被卡在一个庞大的加合物上,此时Mfd就会出现,招募其它修复蛋白,修复DNA损伤部分。这种由Mfd引导的过程被称为转录偶联修复(transcription-coupled repair,生物通译),这种修复在活性转录的DNA链上具有更高的修复速率。

研究人员利用XR-seq方法来分析大肠杆菌细菌细胞中UV诱导的损伤,发现了正常细胞中转录偶联修复的明确证据,但在缺失Mfd的细胞中无法进行这种修复,这证实了Mfd的这一过程中的关键作用。

UvrD

在进一步的实验中,研究人员又发现另外一个切除修复蛋白:UvrD在大肠杆菌中帮助清除受损DNA切除片段的新作用。

如果缺失UvrD,切下的DNA片段就会仍然与染色体DNA结合,使得细胞废物处理酶难以将其切碎降解。同时切除该链的修复蛋白也会绑定在上面,接着切除受损DNA的其它位点。UvrD的工作就是从染色体DNA中解开这些损坏和丢弃的DNA片段,以便可以快速进入下一步处理,相关的修复蛋白也可以继续进行新一轮的修复。

下一步研究人员计划在细菌细胞,人类和其他哺乳动物细胞中利用XR-seq技术解析切除修复的详细过程。

原始出处:

Ogun Adebali, Yi-Ying Chiou, Jinchuan Hu,et al.Genome-wide transcription-coupled repair in Escherichia coli is mediated by the Mfd translocase.PNAS. January 6, 2017.

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    2018-01-10 drwjr
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    2017-02-15 wumeihua90
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    2017-02-15 jambiya
  5. [GetPortalCommentsPageByObjectIdResponse(id=1949297, encodeId=ead0194929e54, content=<a href='/topic/show?id=5ed95833172' target=_blank style='color:#2F92EE;'>#新定义#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58331, encryptionId=5ed95833172, topicName=新定义)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6ab940, createdName=hukaixun, createdTime=Tue Mar 21 09:47:00 CST 2017, time=2017-03-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1855957, encodeId=54f2185595e8f, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Wed Jan 10 10:47:00 CST 2018, time=2018-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1462314, encodeId=b58d146231404, content=<a href='/topic/show?id=5c0c9191e10' target=_blank style='color:#2F92EE;'>#诺奖#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=91917, encryptionId=5c0c9191e10, topicName=诺奖)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c4d36483905, createdName=wumeihua90, createdTime=Wed Feb 15 01:47:00 CST 2017, time=2017-02-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1533712, encodeId=18951533e1252, content=<a href='/topic/show?id=b1b260e6fb' target=_blank style='color:#2F92EE;'>#DNA修复#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6076, encryptionId=b1b260e6fb, topicName=DNA修复)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ff6f12479618, createdName=jambiya, createdTime=Wed Feb 15 01:47:00 CST 2017, time=2017-02-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=175904, encodeId=31ed1e5904bb, content=科学技术在进步, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2d331664955, createdName=老段, createdTime=Mon Feb 13 11:47:23 CST 2017, time=2017-02-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=175896, encodeId=86891e58964d, content=继续努力吧加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/12/31/60fc0213ae09a3dbbba19993663ef4db.jpg, createdBy=33c31971480, createdName=1e160a78m83(暂无匿称), createdTime=Mon Feb 13 11:05:57 CST 2017, time=2017-02-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=175895, encodeId=b5111e589530, content=不太懂!, beContent=null, objectType=article, channel=null, level=null, likeNumber=128, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20230812/e93037ddfed9425fb0316dc3e904f2f4/870c0a4383ef42ef803173fea0339be3.jpg, createdBy=27ba1551982, createdName=huangzh898, createdTime=Mon Feb 13 10:56:41 CST 2017, time=2017-02-13, status=1, ipAttribution=)]
    2017-02-13 老段

    科学技术在进步

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1949297, encodeId=ead0194929e54, content=<a href='/topic/show?id=5ed95833172' target=_blank style='color:#2F92EE;'>#新定义#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58331, encryptionId=5ed95833172, topicName=新定义)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6ab940, createdName=hukaixun, createdTime=Tue Mar 21 09:47:00 CST 2017, time=2017-03-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1855957, encodeId=54f2185595e8f, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Wed Jan 10 10:47:00 CST 2018, time=2018-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1462314, encodeId=b58d146231404, content=<a href='/topic/show?id=5c0c9191e10' target=_blank style='color:#2F92EE;'>#诺奖#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=91917, encryptionId=5c0c9191e10, topicName=诺奖)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c4d36483905, createdName=wumeihua90, createdTime=Wed Feb 15 01:47:00 CST 2017, time=2017-02-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1533712, encodeId=18951533e1252, content=<a href='/topic/show?id=b1b260e6fb' target=_blank style='color:#2F92EE;'>#DNA修复#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6076, encryptionId=b1b260e6fb, topicName=DNA修复)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ff6f12479618, createdName=jambiya, createdTime=Wed Feb 15 01:47:00 CST 2017, time=2017-02-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=175904, encodeId=31ed1e5904bb, content=科学技术在进步, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2d331664955, createdName=老段, createdTime=Mon Feb 13 11:47:23 CST 2017, time=2017-02-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=175896, encodeId=86891e58964d, content=继续努力吧加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/12/31/60fc0213ae09a3dbbba19993663ef4db.jpg, createdBy=33c31971480, createdName=1e160a78m83(暂无匿称), createdTime=Mon Feb 13 11:05:57 CST 2017, time=2017-02-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=175895, encodeId=b5111e589530, content=不太懂!, beContent=null, objectType=article, channel=null, level=null, likeNumber=128, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20230812/e93037ddfed9425fb0316dc3e904f2f4/870c0a4383ef42ef803173fea0339be3.jpg, createdBy=27ba1551982, createdName=huangzh898, createdTime=Mon Feb 13 10:56:41 CST 2017, time=2017-02-13, status=1, ipAttribution=)]
    2017-02-13 1e160a78m83(暂无匿称)

    继续努力吧加油

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1949297, encodeId=ead0194929e54, content=<a href='/topic/show?id=5ed95833172' target=_blank style='color:#2F92EE;'>#新定义#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58331, encryptionId=5ed95833172, topicName=新定义)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6ab940, createdName=hukaixun, createdTime=Tue Mar 21 09:47:00 CST 2017, time=2017-03-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1855957, encodeId=54f2185595e8f, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Wed Jan 10 10:47:00 CST 2018, time=2018-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1462314, encodeId=b58d146231404, content=<a href='/topic/show?id=5c0c9191e10' target=_blank style='color:#2F92EE;'>#诺奖#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=91917, encryptionId=5c0c9191e10, topicName=诺奖)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c4d36483905, createdName=wumeihua90, createdTime=Wed Feb 15 01:47:00 CST 2017, time=2017-02-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1533712, encodeId=18951533e1252, content=<a href='/topic/show?id=b1b260e6fb' target=_blank style='color:#2F92EE;'>#DNA修复#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6076, encryptionId=b1b260e6fb, topicName=DNA修复)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ff6f12479618, createdName=jambiya, createdTime=Wed Feb 15 01:47:00 CST 2017, time=2017-02-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=175904, encodeId=31ed1e5904bb, content=科学技术在进步, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2d331664955, createdName=老段, createdTime=Mon Feb 13 11:47:23 CST 2017, time=2017-02-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=175896, encodeId=86891e58964d, content=继续努力吧加油, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/12/31/60fc0213ae09a3dbbba19993663ef4db.jpg, createdBy=33c31971480, createdName=1e160a78m83(暂无匿称), createdTime=Mon Feb 13 11:05:57 CST 2017, time=2017-02-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=175895, encodeId=b5111e589530, content=不太懂!, beContent=null, objectType=article, channel=null, level=null, likeNumber=128, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20230812/e93037ddfed9425fb0316dc3e904f2f4/870c0a4383ef42ef803173fea0339be3.jpg, createdBy=27ba1551982, createdName=huangzh898, createdTime=Mon Feb 13 10:56:41 CST 2017, time=2017-02-13, status=1, ipAttribution=)]
    2017-02-13 huangzh898

    不太懂!

    0

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