Nature:重磅!饮酒引起的DNA损伤竟可以修复?新方法安全又高效!

2020-03-11 Paris 转化医学网

导语:2018年,《Nature》曾发文指出,酒精(乙醇)代谢产物—乙醛会导致DNA双链断裂,导致染色体重排,并永久地改变DNA序列,从而提高罹患癌症的风险。一石激起千层浪,很多酒精发烧友

导语:2018年,《Nature》曾发文指出,酒精(乙醇)代谢产物—乙醛会导致DNA双链断裂,导致染色体重排,并永久地改变DNA序列,从而提高罹患癌症的风险。一石激起千层浪,很多酒精发烧友为此慢慢远离了各种酒局。

近日,《Nature》再次发文,酒精引起的DNA交联可以通过两种不同的机理修复,有望因此找到治疗FA(范可尼贫血)的策略,甚至降低酒精性癌症的发病率。

乙醛是一种有毒物质,当体内含量过高时,乙醛会堆积在细胞里,造成一种危险的DNA损伤-链间交联(ICL),该损伤将DNA的两条链粘在一起。结果,它阻碍了细胞分裂和蛋白质生产。最终,ICL损伤的积累可能导致细胞死亡和癌症。万幸的是,机体存在自我保护系统,细胞也不例外,可以修复这种类型的DNA损伤。乙醛引起的针对ICL的第一道防线是ALDH2酶,该酶会将乙醛分解成乙酸,然而,大约一半的亚洲人口体内的乙醛脱氢酶2基因突变了,无法正常工作了,所以亚洲人酒精性癌症的发病率很高。
前面我们提到过,乙醛累积会造成DNA损伤,进而引起FA,FA是一种罕见的常染色体或X染色体隐性遗传病,其临床表现为进行性骨髓衰竭、恶性血液系统肿瘤等,该疾病的主要特征是患者DNA发生自发断裂以及交联剂诱导后可产生DNA链间交联(interstand cross-links, ICL)现象。乙醛解毒和FA途径的联合失活诱导突变,加速恶性肿瘤的发展并引起血液干细胞的快速消耗,对于乙醛脱氢酶2基因失活的人而言,身体的第二层自我保护机制就是修复乙醛导致的DNA损伤。然而,乙醛引起的DNA损伤性质及修复问题至今仍是未解之谜。

为此,来自Puck Knipscheer(Hubrecht研究所)和Ketan J. Patel(MRC分子生物学实验室)小组的科学家研究了针对酒精诱导的ICL的第二道防线:修复DNA损伤的机制。研究人员使用爪蛙卵(Xenopus laevis)(生物学研究中常用的动物模型)的卵中提取的蛋白质提取物研究了这些机制。通过使用这些提取物修复乙醛形成的ICL,他们发现了修复ICL损伤的两种机制:其中一种便是已知的Fanconi贫血(FA)途径,目前已鉴定出22种“FANC“蛋白参与该途径,它通过切除来运作—类似于修复化学治疗剂顺铂引起的链见交联机制,然而,与顺铂诱导的交联修复相比,乙醛诱导的交联修复导致突变频率和突变谱改变。除了FA通路,他们还发现了一个更快的修复机制存在,大约有一半的乙醛诱导的DNA交联是未知的修复方式修复的。

FA通路的修复方式:红色短线是DNA交联损伤位点

两种不同修复方式的对比(左下角FA修复方式,右下角是新发现的修复方式)

这两种机制彼此不同:在FA途径中,DNA被切除以去除ICL,而新发现的途径中的酶则在自身中切断了交联,第二种修复机制需要复制叉的融合,但不涉及DNA切口,而且乙醛交联本身被破坏了,研究人员继续深入研究发现,这个未知的修复方式虽然能修复乙醛诱导的DNA交联损伤,但是对于顺铂诱导的DNA交联损伤却无能为力。遗憾的是,虽然找到了修复方式,但研究人员对于其背后的机制还未曾有进一步的认识,但不可否认的是,这无疑是修复DNA损伤的“新开关”,开关找到了,钥匙早晚也会被找到,那么假以时日,FA治疗相关药物的研发都不再是空谈。

可以说,该研究为酒精打了一场翻身仗,但还是要提醒大家,这篇文章并不能作为我们重拾酒杯的借口,无论怎样,饮酒都要适度!

原始出处:

Michael R. Hodskinson, Alice Bolner, Koichi Sato, et.al. Alcohol-derived DNA crosslinks are repaired by two distinct mechanisms. Nature 04 March 2020

版权声明:
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章,或“梅斯号”自媒体发布的文章,仅系出于传递更多信息之目的,本站仅负责审核内容合规,其内容不代表本站立场,本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
评论区 (5)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1903399, encodeId=0def19033991d, content=<a href='/topic/show?id=e1b0583884b' target=_blank style='color:#2F92EE;'>#新方法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58388, encryptionId=e1b0583884b, topicName=新方法)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c22f171, createdName=kord1982, createdTime=Mon Aug 17 14:39:53 CST 2020, time=2020-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1884153, encodeId=95b3188415308, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Wed Sep 09 09:39:53 CST 2020, time=2020-09-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1397927, encodeId=9180139e92789, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eoNX3lUOlDKGBUEPNwZx0nibmdcFyeibnX4WMhUSCU2REpGRWtSmnT2CCs0dA5waxvJknYDxwtYnIcQ/132, createdBy=294e2500218, createdName=ms3046638856685384, createdTime=Thu Mar 12 23:39:53 CST 2020, time=2020-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1455051, encodeId=2ed214550519c, content=<a href='/topic/show?id=4f4a6103d8' target=_blank style='color:#2F92EE;'>#DNA损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6103, encryptionId=4f4a6103d8, topicName=DNA损伤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=758a5627999, createdName=makuansheng, createdTime=Thu Mar 12 23:39:53 CST 2020, time=2020-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1549560, encodeId=e527154956022, content=<a href='/topic/show?id=f7879600061' target=_blank style='color:#2F92EE;'>#重磅#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96000, encryptionId=f7879600061, topicName=重磅)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3acc14121561, createdName=xxxx1054, createdTime=Thu Mar 12 23:39:53 CST 2020, time=2020-03-12, status=1, ipAttribution=)]
  2. [GetPortalCommentsPageByObjectIdResponse(id=1903399, encodeId=0def19033991d, content=<a href='/topic/show?id=e1b0583884b' target=_blank style='color:#2F92EE;'>#新方法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58388, encryptionId=e1b0583884b, topicName=新方法)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c22f171, createdName=kord1982, createdTime=Mon Aug 17 14:39:53 CST 2020, time=2020-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1884153, encodeId=95b3188415308, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Wed Sep 09 09:39:53 CST 2020, time=2020-09-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1397927, encodeId=9180139e92789, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eoNX3lUOlDKGBUEPNwZx0nibmdcFyeibnX4WMhUSCU2REpGRWtSmnT2CCs0dA5waxvJknYDxwtYnIcQ/132, createdBy=294e2500218, createdName=ms3046638856685384, createdTime=Thu Mar 12 23:39:53 CST 2020, time=2020-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1455051, encodeId=2ed214550519c, content=<a href='/topic/show?id=4f4a6103d8' target=_blank style='color:#2F92EE;'>#DNA损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6103, encryptionId=4f4a6103d8, topicName=DNA损伤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=758a5627999, createdName=makuansheng, createdTime=Thu Mar 12 23:39:53 CST 2020, time=2020-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1549560, encodeId=e527154956022, content=<a href='/topic/show?id=f7879600061' target=_blank style='color:#2F92EE;'>#重磅#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96000, encryptionId=f7879600061, topicName=重磅)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3acc14121561, createdName=xxxx1054, createdTime=Thu Mar 12 23:39:53 CST 2020, time=2020-03-12, status=1, ipAttribution=)]
    2020-09-09 liye789132251
  3. [GetPortalCommentsPageByObjectIdResponse(id=1903399, encodeId=0def19033991d, content=<a href='/topic/show?id=e1b0583884b' target=_blank style='color:#2F92EE;'>#新方法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58388, encryptionId=e1b0583884b, topicName=新方法)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c22f171, createdName=kord1982, createdTime=Mon Aug 17 14:39:53 CST 2020, time=2020-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1884153, encodeId=95b3188415308, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Wed Sep 09 09:39:53 CST 2020, time=2020-09-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1397927, encodeId=9180139e92789, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eoNX3lUOlDKGBUEPNwZx0nibmdcFyeibnX4WMhUSCU2REpGRWtSmnT2CCs0dA5waxvJknYDxwtYnIcQ/132, createdBy=294e2500218, createdName=ms3046638856685384, createdTime=Thu Mar 12 23:39:53 CST 2020, time=2020-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1455051, encodeId=2ed214550519c, content=<a href='/topic/show?id=4f4a6103d8' target=_blank style='color:#2F92EE;'>#DNA损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6103, encryptionId=4f4a6103d8, topicName=DNA损伤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=758a5627999, createdName=makuansheng, createdTime=Thu Mar 12 23:39:53 CST 2020, time=2020-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1549560, encodeId=e527154956022, content=<a href='/topic/show?id=f7879600061' target=_blank style='color:#2F92EE;'>#重磅#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96000, encryptionId=f7879600061, topicName=重磅)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3acc14121561, createdName=xxxx1054, createdTime=Thu Mar 12 23:39:53 CST 2020, time=2020-03-12, status=1, ipAttribution=)]
  4. [GetPortalCommentsPageByObjectIdResponse(id=1903399, encodeId=0def19033991d, content=<a href='/topic/show?id=e1b0583884b' target=_blank style='color:#2F92EE;'>#新方法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58388, encryptionId=e1b0583884b, topicName=新方法)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c22f171, createdName=kord1982, createdTime=Mon Aug 17 14:39:53 CST 2020, time=2020-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1884153, encodeId=95b3188415308, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Wed Sep 09 09:39:53 CST 2020, time=2020-09-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1397927, encodeId=9180139e92789, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eoNX3lUOlDKGBUEPNwZx0nibmdcFyeibnX4WMhUSCU2REpGRWtSmnT2CCs0dA5waxvJknYDxwtYnIcQ/132, createdBy=294e2500218, createdName=ms3046638856685384, createdTime=Thu Mar 12 23:39:53 CST 2020, time=2020-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1455051, encodeId=2ed214550519c, content=<a href='/topic/show?id=4f4a6103d8' target=_blank style='color:#2F92EE;'>#DNA损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6103, encryptionId=4f4a6103d8, topicName=DNA损伤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=758a5627999, createdName=makuansheng, createdTime=Thu Mar 12 23:39:53 CST 2020, time=2020-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1549560, encodeId=e527154956022, content=<a href='/topic/show?id=f7879600061' target=_blank style='color:#2F92EE;'>#重磅#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96000, encryptionId=f7879600061, topicName=重磅)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3acc14121561, createdName=xxxx1054, createdTime=Thu Mar 12 23:39:53 CST 2020, time=2020-03-12, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1903399, encodeId=0def19033991d, content=<a href='/topic/show?id=e1b0583884b' target=_blank style='color:#2F92EE;'>#新方法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58388, encryptionId=e1b0583884b, topicName=新方法)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c22f171, createdName=kord1982, createdTime=Mon Aug 17 14:39:53 CST 2020, time=2020-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1884153, encodeId=95b3188415308, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Wed Sep 09 09:39:53 CST 2020, time=2020-09-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1397927, encodeId=9180139e92789, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eoNX3lUOlDKGBUEPNwZx0nibmdcFyeibnX4WMhUSCU2REpGRWtSmnT2CCs0dA5waxvJknYDxwtYnIcQ/132, createdBy=294e2500218, createdName=ms3046638856685384, createdTime=Thu Mar 12 23:39:53 CST 2020, time=2020-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1455051, encodeId=2ed214550519c, content=<a href='/topic/show?id=4f4a6103d8' target=_blank style='color:#2F92EE;'>#DNA损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6103, encryptionId=4f4a6103d8, topicName=DNA损伤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=758a5627999, createdName=makuansheng, createdTime=Thu Mar 12 23:39:53 CST 2020, time=2020-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1549560, encodeId=e527154956022, content=<a href='/topic/show?id=f7879600061' target=_blank style='color:#2F92EE;'>#重磅#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96000, encryptionId=f7879600061, topicName=重磅)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3acc14121561, createdName=xxxx1054, createdTime=Thu Mar 12 23:39:53 CST 2020, time=2020-03-12, status=1, ipAttribution=)]
    2020-03-12 xxxx1054

相关资讯

BMJ:酒类很低销售限价与酒精消费

实行最低单位价格成功地减少了苏格兰家庭购买酒精的数量

男士孕前3月饮酒,孩子易患先心病

怀孕前后,为了娃健康,通常娃妈备受关注,殊不知娃爹也很关键。近期,中南大学湘雅公共卫生学院Jiabi Qin等对55项研究进行分析表明:戒酒很重要,不论父母,在怀孕前后三个月饮酒均会增加胎儿得先天性心脏病的风险,尤其是父亲。

“酒后用头孢”和“用头孢后饮酒”,结局大不同!

如今很多人都知道饮酒的同时使用头孢类药物会产生双硫仑样反应,严重时会危及生命。我是呼吸科临床药师,工作中发现“饮酒后多久可以使用头孢?”和“使用头孢后多久可以饮酒?”这两个问题常被混淆。

Eur J Preven Cardio:备孕期间,准爸爸和准妈妈都应该戒酒!来看全新Meta分析结果

长期以来,女性在备孕和孕期一直被告知要避免饮酒,但人们对父亲饮酒是否会影响精子质量、进而影响孩子健康的关注却相对少得多。

全面利弊解析!生活方式如何影响心脏健康|GW-ICC2019

关于生活方式与心血管健康,看看GW-ICC2019大会上有哪些最新内容~

喝啤酒导致啤酒肚是被诬陷?任何频率饮酒都可致腹型肥胖

饮酒会让人变胖吗?啤酒比白酒、葡萄酒更容易催生“啤酒肚”?近期中国慢性前瞻性研究的一项最新分析给出了答案。