UBC13, a DNA-damage-inducible gene, is a member of the error-free postreplication repair pathway in Saccharomyces cerevisiae
UBC13, a DNA-damage-inducible gene, is a member of the error-free postreplication repair pathway in Saccharomyces cerevisiae
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DOI：
10.1007/s002940050515
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发表时间：
2000-03-01
期刊：
影响因子：
2.5
通讯作者：
Xiao, W
中科院分区：
文献类型：
--
作者：
Brusky, J;Zhu, Y;Xiao, W
Ubc 13蛋白最近被鉴定为在Ub Lys-63残基而不是常规的Lys-48残基处在泛素（Ub）链组装中具有独特的作用。这种活性需要Ubc 13与Mms 2形成复合物，实际上，Ubc 13和Mms 2突变在其他地方已经显示出对UV敏感性的上位性。已知MMS 2基因是无错误DNA复制后修复（PRR）途径的成员。相比之下，Ub Lys-63残基先前已经涉及易错PRR途径，因为携带ubiK 63 R突变的酵母细胞在UV诱导的诱变中是有缺陷的。在本研究中，我们试图确定UBC 13在PRR通路中的作用。我们发现ubc 13突变对mms 2和rad 6具有上位性，证实了UBC 13属于PRR途径。我们还发现ubc 13与易错PRR途径突变rev 3具有协同作用，表明UBC 13处于REV 3诱变的替代途径中。ubc 13突变体显示自发突变率增加高达30倍，并且这种增加在很大程度上依赖于REV 3。此外，紫外线诱导的诱变是完全功能的ubc 13突变体。这些结果共同证明UBC 13是无错误PRR途径的成员。UBC 13参与对DNA损伤的细胞耐受性进一步被我们的发现所暗示，即UBC 13转录物水平响应于DNA损伤而增加高达6倍。
The Ubc13 protein was recently identified for its unique role in ubiquitin (Ub) chain assembly at the Ub Lys-63 residue instead of the conventional Lys-48 residue. This activity requires Ubc13 to form a complex with Mms2 and indeed ubc13 and mms2 mutations have been shown elsewhere to be epistatic with respect to UV sensitivity. The MMS2 gene is known to be a member of the error-free DNA postreplication repair (PRR) pathway. By contrast, the Ub Lys-63 residue has been previously implicated in the error-prone PRR pathway, since yeast cells carrying the ubiK63R mutation are defective in UV-induced mutagenesis. In the present study, we attempted to define the role of UBC13 within the PRR pathway. We found that the ubc13 mutation is epistatic to mms2 and rad6, confirming that UBC13 belongs to the PRR-pathway. We also found that ubc13 is synergistic to the error-prone PRR pathway mutation rev3, indicating that UBC13 is in a pathway alternative to REV3 mutagenesis. The ubc13 mutant displays up to a 30-fold increase in the spontaneous mutation rate, and this increase is largely REV3 dependent. In addition, UV-induced mutagenesis is fully functional in the ubc13 mutant. These results together demonstrate that UBC13 is a member of the error-free PRR pathway. The involvement of UBC13 in cellular tolerance to DNA-damage is further implicated by our finding that the UBC13 transcript level is increased up to 6-fold in response to DNA-damage.