Comparison of functional properties of mammalian DNA polymerase λ and DNA polymerase β in reactions of DNA synthesis related to DNA repair
- 作者：Natalia A. Lebedeva ; Nadejda I. Rechkunova ; Sergey V. Dezhurov ; Svetlana N. Khodyreva ; Alain Favre ; Luis Blanco and Olga I. Lavrik
- 关键词：DNA polymerase λ ; DNA polymerase β ; Flap-endonuclease-1 ; Apurinic/apyrimidinic endonuclease-1 ; Base excision repair
- 刊名：Biochimica et Biophysica Acta - Proteins and Proteomics
- 出版年：2005
- 期刊代码：161_15709639
- 类别：bio
- 出版时间：2005
- 卷：1751
- 期：2
- 页码：150-158
- 文件大小：567 K
摘要
DNA polymerase λ (Pol λ) is a novel enzyme of the family X of DNA polymerases. Pol λ has some properties in common with DNA polymerase β (Pol β). The substrate properties of Pol λ were compared to Pol β using DNAs mimicking short-patch (SP) and long-patch (LP) base excision repair (BER) intermediates as well as recessed template primers. In the present work, the influence of several BER proteins such as flap-endonuclease-1 (FEN1), PCNA, and apurinic/apyrimidinic endonuclease-1 (APE1) on the activity of Pol λ was investigated. Pol λ is unable to catalyze strand displacement synthesis using nicked DNA, although this enzyme efficiently incorporates a dNMP into a one-nucleotide gap. FEN1 and PCNA stimulate the strand displacement activity of Pol λ. FEN1 processes nicked DNA, thus removing a barrier to Pol λ DNA synthesis. It results in a one-nucleotide gapped DNA molecule that is a favorite substrate of Pol λ. Photocrosslinking and functional assay show that Pol λ is less efficient than Pol β in binding to nicked DNA. APE1 has no influence on the strand displacement activity of Pol λ though it stimulates strand displacement synthesis catalyzed with Pol β. It is suggested that Pol λ plays a role in the SP BER rather than contributes to the LP BER pathway.