Sterling Catherine H, Sweasy Joann B
Department of Therapeutic Radiology and Genetics, Yale University, New Haven, Connecticut 06510, USA.
Genetics. 2006 Jan;172(1):89-98. doi: 10.1534/genetics.105.049254. Epub 2005 Oct 11.
The DNA polymerase 4 protein (Pol4) of Saccharomyces cerevisiae is a member of the X family of DNA polymerases whose closest human relative appears to be DNA polymerase lambda. Results from previous genetic studies conflict over the role of Pol4 in vivo. Here we show that deletion of Pol4 in a diploid strain of the SK1 genetic background results in sensitivity to methyl methanesulfonate (MMS). However, deletion of Pol4 in other strain backgrounds and in haploid strains does not yield an observable phenotype. The MMS sensitivity of a Pol4-deficient strain can be rescued by deletion of YKu70. We also show that deletion of Pol4 results in a 6- to 14-fold increase in the MMS-induced mutation frequency and in a significant increase in AT-to-TA transversions. Our studies suggest that Pol4 is critical for accurate repair of DNA lesions induced by MMS.
酿酒酵母的DNA聚合酶4蛋白（Pol4）是DNA聚合酶X家族的成员，其在人类中最接近的亲属似乎是DNA聚合酶λ。先前的遗传学研究结果在Pol4在体内的作用方面存在冲突。在这里，我们表明，在SK1遗传背景的二倍体菌株中删除Pol4会导致对甲磺酸甲酯（MMS）敏感。然而，在其他菌株背景和单倍体菌株中删除Pol4不会产生可观察到的表型。Pol4缺陷菌株对MMS的敏感性可以通过删除YKu70来挽救。我们还表明，删除Pol4会导致MMS诱导的突变频率增加6至14倍，并且AT到TA的颠换显著增加。我们的研究表明，Pol4对于准确修复由MMS诱导的DNA损伤至关重要。
