Erlich Rachel L, Fry Rebecca C, Begley Thomas J, Daee Danielle L, Lahue Robert S, Samson Leona D
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
PLoS One. 2008;3(11):e3717. doi: 10.1371/journal.pone.0003717. Epub 2008 Nov 13.
Yeast strains lacking Anc1, a member of the YEATS protein family, are sensitive to several DNA damaging agents. The YEATS family includes two human genes that are common fusion partners with MLL in human acute leukemias. Anc1 is a member of seven multi-protein complexes involved in transcription, and the damage sensitivity observed in anc1Delta cells is mirrored in strains deleted for some other non-essential members of several of these complexes. Here we show that ANC1 is in the same epistasis group as SRS2 and RAD5, members of the postreplication repair (PRR) pathway, but has additive or synergistic interactions with several other members of this pathway. Although PRR is traditionally divided into an "error-prone" and an "error-free" branch, ANC1 is not epistatic with all members of either established branch, and instead defines a new error-free branch of the PRR pathway. Like several genes involved in PRR, an intact ANC1 gene significantly suppresses spontaneous mutation rates, including the expansion of (CAG)(25) repeats. Anc1's role in the PRR pathway, as well as its role in suppressing triplet repeats, point to a possible mechanism for a protein of potential medical interest.
缺乏YEATS蛋白家族成员Anc1的酵母菌株对多种DNA损伤剂敏感。YEATS家族包括两个人类基因,它们是人类急性白血病中与MLL常见的融合伴侣。Anc1是参与转录的七个多蛋白复合物的成员之一,在anc1Δ细胞中观察到的损伤敏感性在缺失这些复合物中其他一些非必需成员的菌株中也有体现。在这里,我们表明ANC1与复制后修复(PRR)途径的成员SRS2和RAD5处于同一上位性组,但与该途径的其他几个成员具有累加或协同相互作用。尽管PRR传统上分为“易出错”和“无差错”两个分支,但ANC1与任何一个既定分支的所有成员都不存在上位性,而是定义了PRR途径一个新的无差错分支。与几个参与PRR的基因一样,完整的ANC1基因能显著抑制自发突变率,包括(CAG)(25)重复序列的扩增。Anc1在PRR途径中的作用,以及其在抑制三联体重复序列中的作用,为一种具有潜在医学意义的蛋白质指出了一种可能的机制。