Recognition and repair of the cyclobutane thymine dimer, a major cause of skin cancers, by the human excision nuclease

Author:

Reardon Joyce T.,Sancar Aziz

Abstract

The cyclobutane thymine dimer is the major DNA lesion induced in human skin by sunlight and is a primary cause of skin cancer, the most prevalent form of cancer in the Northern Hemisphere. In humans, the only known cellular repair mechanism for eliminating the dimer from DNA is nucleotide excision repair. Yet the mechanism by which the dimer is recognized and removed by this repair system is not known. Here we demonstrate that the six-factor human excision nuclease recognizes and removes the dimer at a rate consistent with the in vivo rate of removal of this lesion, even though none of the six factors alone is capable of efficiently discriminating the dimer from undamaged DNA. We propose a recognition mechanism by which the low-specificity recognition factors, RPA, XPA, and XPC, act in a cooperative manner to locate the lesion and, aided by the kinetic proofreading provided by TFIIH, form a high-specificity complex at the damage site that initiates removal of thymine dimers at a physiologically relevant rate and specificity.

Publisher

Cold Spring Harbor Laboratory

Subject

Developmental Biology,Genetics

Cited by 161 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3