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跨损伤 DNA 聚合酶可能参与酵母减数分裂。

Trans-Lesion DNA Polymerases May Be Involved in Yeast Meiosis.

机构信息

Department of Genetics, The Hebrew University of Jerusalem, Jerusalem 91904, Israel

Department of Medical Laboratory Sciences, Hadassah Academic College, Jerusalem 91010, Israel.

出版信息

G3 (Bethesda). 2013 Apr 9;3(4):633-644. doi: 10.1534/g3.113.005603.

Abstract

Trans-lesion DNA polymerases (TLSPs) enable bypass of DNA lesions during replication and are also induced under stress conditions. Being only weakly dependent on their template during replication, TLSPs introduce mutations into DNA. The low processivity of these enzymes ensures that they fall off their template after a few bases are synthesized and are then replaced by the more accurate replicative polymerase. We find that the three TLSPs of budding yeast Saccharomyces cerevisiae Rev1, PolZeta (Rev3 and Rev7), and Rad30 are induced during meiosis at a time when DNA double-strand breaks (DSBs) are formed and homologous chromosomes recombine. Strains deleted for one or any combination of the three TLSPs undergo normal meiosis. However, in the triple-deletion mutant, there is a reduction in both allelic and ectopic recombination. We suggest that trans-lesion polymerases are involved in the processing of meiotic double-strand breaks that lead to mutations. In support of this notion, we report significant yeast two-hybrid (Y2H) associations in meiosis-arrested cells between the TLSPs and DSB proteins Rev1-Spo11, Rev1-Mei4, and Rev7-Rec114, as well as between Rev1 and Rad30 We suggest that the involvement of TLSPs in processing of meiotic DSBs could be responsible for the considerably higher frequency of mutations reported during meiosis compared with that found in mitotically dividing cells, and therefore may contribute to faster evolutionary divergence than previously assumed.

摘要

跨损伤 DNA 聚合酶(TLSPs)能够在复制过程中绕过 DNA 损伤,并在应激条件下被诱导。在复制过程中,TLSPs 对其模板的依赖性较弱,会将突变引入 DNA 中。这些酶的低延伸性确保它们在合成几个碱基后就会从模板上脱落,然后由更准确的复制聚合酶取代。我们发现,芽殖酵母酿酒酵母中的三种 TLSPs,即 Rev1、PolZeta(Rev3 和 Rev7)和 Rad30,在减数分裂期间被诱导,此时会形成 DNA 双链断裂(DSB)并发生同源染色体重组。缺失一种或任意两种 TLSP 的菌株仍能正常进行减数分裂。然而,在三缺失突变体中,等位基因重组和异位重组都减少了。我们认为,跨损伤聚合酶参与了导致突变的减数分裂双链断裂的处理。为了支持这一观点,我们报告称,在减数分裂停滞细胞中,TLSP 与 DSB 蛋白 Rev1-Spo11、Rev1-Mei4 和 Rev7-Rec114 之间,以及 Rev1 和 Rad30 之间存在显著的酵母双杂交(Y2H)关联。我们认为,TLSPs 参与减数分裂 DSB 的处理可能是导致减数分裂中突变频率明显高于有丝分裂细胞的原因,因此可能比之前认为的更有助于更快的进化分歧。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d55/3618350/6541ef92dc91/633f1.jpg

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