Okazaki fragment maturation:nucleases take centre stage

作     者：Li Zheng Binghui Shen 

作者机构：Department of Cancer BiologyCity of Hope National Medical Center and Beckman Research InstituteDuarteCA 91010USA 

出 版 物：《分子细胞生物学报:英文版》 (Journal of Molecular Cell Biology)

年 卷 期：2011年第3卷第1期

页      面：23-30页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Cancer Institute grants R01CA073764 and R01CA085344 

主　　题：Okazaki fragment maturation FEN1 DNA2 PCNA RPA cancer 

摘      要：Completion of lagging strand DNA synthesis requires processing of up to 50 million Okazaki fragments per cell cycle in mammalian *** in yeast,the Okazaki fragment maturation happens approximately a million times during a single round of DNA ***,efficient processing of Okazaki fragments is vital for DNA replication and cell *** this process,primase-synthesized RNA/DNA primers are removed,and Okazaki fragments are joined into an intact lagging strand *** processing of RNA/DNA primers requires a group of structure-specific nucleases typified by flap endonuclease 1(FEN1).Here,we sum-marize the distinct roles of these nucleases in different pathways for removal of RNA/DNA *** findings reveal that Okazaki fragment maturation is highly *** dynamic interactions of polymerase d,FEN1 and DNA ligase I with prolif-erating cell nuclear antigen allow these enzymes to act sequentially during Okazaki fragment *** protein–protein interactions may be regulated by post-translational *** also discuss studies using mutant mouse models that suggest two distinct cancer etiological mechanisms arising from defects in different steps of Okazaki fragment *** that affect the efficiency of RNA primer removal may result in accumulation of unligated nicks and DNA double-strand *** DNA strand breaks can cause varying forms of chromosome aberrations,contributing to development of cancer that associates with aneuploidy and gross chromosomal *** the other hand,mutations that impair editing out of polymerase a incorporation errors result in cancer displaying a strong mutator phenotype.