Tyrosyl-DNA phosphodiesterase 1 initiates repair of apurinic/apyrimidinic sites

详细信息	查看全文 | 推荐本文 |

• 作者：Natalia A. Lebedeva^a ; Nadejda I. Rechkunova^a ; Sherif F. El-Khamisy^b ; ^c ; ² ; ^{smfame20@sussex.ac.uk} ; Olga I. Lavrik^a ; ¹ ; ^{lavrik@niboch.nsc.ru}
• 关键词：Base excision repair ; AP site ; Tyrosyl-DNA phosphodiesterase 1
• 刊名：Biochimie
• 出版年：2012
• 期刊代码：24_03009084
• 类别：bio
• 出版时间：August, 2012
• 卷：94
• 期：8
• 页码：1749-1753
• 文件大小：637 K

摘要

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) catalyzes the hydrolysis of the phosphodiester linkage between the DNA 3鈥?phosphate and a tyrosine residue as well as a variety of other DNA 3鈥?damaged termini. Recently we have shown that Tdp1 can liberate the 3鈥?DNA phosphate termini from apurinic/apyrimidinic (AP) sites. Here, we found that Tdp1 is more active in the cleavage of the AP sites inside bubble-DNA structure in comparison to ssDNA containing AP site. Furthermore, Tdp1 hydrolyzes AP sites opposite to bulky fluorescein adduct faster than AP sites located in dsDNA. Whilst the Tdp1 H493R (SCAN1) and H263A mutants retain the ability to bind an AP site-containing DNA, both mutants do not reveal endonuclease activity, further suggesting the specificity of the AP cleavage activity. We suggest that this Tdp1 activity can contribute to the repair of AP sites particularly in DNA structures containing ssDNA region or AP sites in the context of clustered DNA lesions.