1月3日，國(guó)際著名雜志Cell Research在線刊登了中科院遺傳與發(fā)育生物學(xué)研究所楊崇林研究組的最新研究成果“MRG-1 is required for genomic integrity in Caenorhabditis elegans germ cells,，”,，文章中，作者揭示了其在細(xì)胞凋亡及基因組穩(wěn)定性研究中取得的新進(jìn)展,。
基因組穩(wěn)定性對(duì)于真核生物的正常生長(zhǎng)發(fā)育以及增殖是必不可少的前提條件,。然而，在生存過(guò)程中,，生物體基因組由于經(jīng)常受到一些內(nèi)在和外在因素的影響,，造成各種形式的DNA損傷。為了保持基因組的穩(wěn)定性,，真核生物中已經(jīng)形成了一種在進(jìn)化上高度保守的機(jī)制,，來(lái)修復(fù)應(yīng)對(duì)各種DNA損傷。當(dāng)DNA損傷嚴(yán)重到無(wú)法正確修復(fù)時(shí),，細(xì)胞會(huì)啟動(dòng)凋亡程序來(lái)避免受損細(xì)胞的大量增殖,。維持基因組穩(wěn)定性對(duì)于生物個(gè)體通過(guò)減數(shù)分裂將遺傳信息準(zhǔn)確地傳遞給子代是至關(guān)重要的,。
中科院遺傳與發(fā)育生物學(xué)研究所楊崇林研究組以秀麗線蟲為模式,，發(fā)現(xiàn)了一個(gè)對(duì)基因組穩(wěn)定性維持起重要作用的基因mrg-1，其人類同源基因?yàn)镸rg15,。在線蟲mrg-1突變體的生殖腺中,，細(xì)胞凋亡明顯增多且可被DNA損傷修復(fù)和同源染色體聯(lián)會(huì)的檢查點(diǎn)基因的突變抑制,。在mrg-1突變體的生殖腺細(xì)胞中，雙鏈斷裂DNA增多,。在外源DNA損傷誘導(dǎo)后,，mrg-1突變體生殖腺的終變期細(xì)胞發(fā)生高比例的染色體斷裂。
研究還發(fā)現(xiàn),，在mrg-1的突變體性腺中,，本應(yīng)該呈現(xiàn)粗線期特征的細(xì)胞多停滯于細(xì)線期/偶線期，且這些細(xì)胞中組蛋白H3的第九位賴氨酸上的雙甲基化（H3K9me2）的水平顯著上調(diào),，這種表型與聯(lián)會(huì)復(fù)合體組分的缺失突變體相似,。這表明mrg-1的缺失使聯(lián)會(huì)的正常進(jìn)行受到了阻礙。此外,，通過(guò)與本所程祝寬研究組的合作,，他們發(fā)現(xiàn)在減數(shù)分裂的早期，mrg-1突變體中的同源染色體部分出現(xiàn)配對(duì)問(wèn)題,。這些結(jié)果表明,，MRG-1通過(guò)促進(jìn)DNA損傷的修復(fù)和同源染色體聯(lián)會(huì)的正常進(jìn)行，對(duì)基因組穩(wěn)定性的維持發(fā)揮著重要作用,。
博士研究生徐晶為該論文的第一作者,。楊崇林博士為中國(guó)科學(xué)院“百人計(jì)劃”入選者，其實(shí)驗(yàn)室的研究工作還受到國(guó)家自然科學(xué)基金以及科技部重大科學(xué)研究計(jì)劃資助,。（生物谷Bioon.com）
doi:10.1038/cr.2012.2
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MRG-1 is required for genomic integrity in Caenorhabditis elegans germ cells
Jing Xu, Xiaojuan Sun, Yudong Jing, Mo Wang, Kai Liu, Youli Jian, Mei Yang, Zhukuan Cheng and Chonglin Yang
During meiotic cell division, proper chromosome synapsis and accurate repair of DNA double strand breaks (DSBs) are required to maintain genomic integrity, loss of which leads to apoptosis or meiotic defects. The mechanisms underlying meiotic chromosome synapsis, DSB repair and apoptosis are not fully understood. Here, we report that the chromodomain-containing protein MRG-1 is an important factor for genomic integrity in meiosis in Caenorhabditis elegans. Loss of mrg-1 function resulted in a significant increase in germ cell apoptosis that was partially inhibited by mutations affecting DNA damage checkpoint genes. Consistently, mrg-1 mutant germ lines exhibited SPO-11-generated DSBs and elevated exogenous DNA damage-induced chromosome fragmentation at diakinesis. In addition, the excessive apoptosis in mrg-1 mutants was partially suppressed by loss of the synapsis checkpoint gene pch-2, and a significant number of meiotic nuclei accumulated at the leptotene/zygotene stages with an elevated level of H3K9me2 on the chromatin, which was similarly observed in mutants deficient in the synaptonemal complex, suggesting that the proper progression of chromosome synapsis is likely impaired in the absence of mrg-1. Altogether, these findings suggest that MRG-1 is critical for genomic integrity by promoting meiotic DSB repair and synapsis progression in meiosis.
