研究人员在11月在线出版的《自然—结构和分子生物学》（Nature-Structural Molecular biology）期刊中报告说，他们进一步理解了健康细胞是如何处理抗癌药物所造成的损害的。
转录过程是指遗传信息从DNA转移到RNA的过程，在绝大多数情况下，这一过程会产生一种特别的蛋白质。由部分抗癌药物所引发的DNA损伤会导致转录过程中RNA出错，产生可能有害于细胞的错误蛋白质。
顺铂(cisplatin)是一种常用的化学治疗药物。Patrick Cramer和同事研究了转录机制如何避免由顺铂导致的DNA损伤。他们发现，顺铂损伤会迫使转录过程在受到损害前停止，这种转录过程的“中止”触发了一种能移走毒性损伤的DNA修复通道。（科学时报）
原始出处:
Nature-Structural Molecular biology
Published online: 11 November 2007; | doi:10.1038/nsmb1314
Mechanism of transcriptional stalling at cisplatin-damaged DNA
Gerke E Damsma1, 2, Aaron Alt1, Florian Brueckner1, 2, Thomas Carell1 & Patrick Cramer1, 2
1 Center for Integrated Protein Science CIPSM, Department of Chemistry and Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
2 Gene Center Munich, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
Correspondence should be addressed to Thomas Carell thomas.carell@cup.uni-muenchen.de or Patrick Cramer cramer@LMB.uni-muenchen.de
The anticancer drug cisplatin forms 1,2-d(GpG) DNA intrastrand cross-links (cisplatin lesions) that stall RNA polymerase II (Pol II) and trigger transcription-coupled DNA repair. Here we present a structure-function analysis of Pol II stalling at a cisplatin lesion in the DNA template. Pol II stalling results from a translocation barrier that prevents delivery of the lesion to the active site. AMP misincorporation occurs at the barrier and also at an abasic site, suggesting that it arises from nontemplated synthesis according to an 'A-rule' known for DNA polymerases. Pol II can bypass a cisplatin lesion that is artificially placed beyond the translocation barrier, even in the presence of a GA mismatch. Thus, the barrier prevents transcriptional mutagenesis. The stalling mechanism differs from that of Pol II stalling at a photolesion, which involves delivery of the lesion to the active site and lesion-templated misincorporation that blocks transcription.
