Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in . gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site VSports app下载. .

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. V体育官网.

. 2007 Nov 9;318(5852):967-70.
doi: 10.1126/science.1148242.

"V体育官网入口" Bypass of DNA lesions generated during anticancer treatment with cisplatin by DNA polymerase eta

Aaron Alt  1 , Katja Lammens, Claudia Chiocchini, Alfred Lammens, J Carsten Pieck, David Kuch, Karl-Peter Hopfner, Thomas Carell
Affiliations

Bypass of DNA lesions generated during anticancer treatment with cisplatin by DNA polymerase eta

"VSports" Aaron Alt et al. Science. .

Abstract

DNA polymerase eta (Pol eta) is a eukaryotic lesion bypass polymerase that helps organisms to survive exposure to ultraviolet (UV) radiation, and tumor cells to gain resistance against cisplatin-based chemotherapy. It allows cells to replicate across cross-link lesions such as 1,2-d(GpG) cisplatin adducts (Pt-GG) and UV-induced cis-syn thymine dimers. We present structural and biochemical analysis of how Pol eta copies Pt-GG-containing DNA. The damaged DNA is bound in an open DNA binding rim. Nucleotidyl transfer requires the DNA to rotate into an active conformation, driven by hydrogen bonding of the templating base to the dNTP. For the 3'dG of the Pt-GG, this step is accomplished by a Watson-Crick base pair to dCTP and is biochemically efficient and accurate VSports手机版. In contrast, bypass of the 5'dG of the Pt-GG is less efficient and promiscuous for dCTP and dATP as a result of the presence of the rigid Pt cross-link. Our analysis reveals the set of structural features that enable Pol eta to replicate across strongly distorting DNA lesions. .

PubMed Disclaimer

Publication types (VSports手机版)

MeSH terms