Meiotic Recombination and DNA Repair in Drosophila
Meiotic Recombination and DNA Repair in Drosophila
批准号:
0132655
负责人:
Jeff Sekelsky
金额:
$43.72万
依托单位国家:
美国
项目类别:
Continuing Grant
财政年份:
2002
资助国家:
美国
项目状态:
已结题
起止时间:
2002-05-01 至 2006-04-30
中文摘要
细胞修复DNA链间交联的机制在很大程度上仍然未知。在哺乳动物中,核苷酸切除修复内切酶XPF-Ercc1在链间交联修复中起关键作用。这个功能在果蝇XPF同源基因MEI-9中是保守的。本项目关注MEI-9与新发现的交联修复蛋白MUS312之间的相互作用。将对mus312突变体进行遗传分析,以更好地了解哪些修复和重组途径需要mus312,以及mus312和mei-9在相同途径中的作用程度。为了更好地了解mus312蛋白,将产生mus312的其他等位基因。mei-9和mus312对于减数分裂交叉的产生也是必不可少的,这一功能也将在遗传和分子上进行研究。DNA不断受到内部和外部因素的攻击;一些化疗药物通过在DNA中产生链间交联来发挥作用。正常细胞修复这种损伤的机制尚不清楚。目前的研究旨在了解两个关键蛋白MEI-9和MUS312对这种修复的贡献。这些蛋白质相互作用,在果蝇体内进行修复过程。
英文摘要
The mechanisms by which cells repair DNA interstrand crosslinks remain largely unknown. In mammals, the nucleotide excision repair endonuclease XPF-Ercc1 plays a key role in interstrand crosslink repair. This function is conserved in the Drosophila XPF homolog MEI-9. This project concerns the interaction between MEI-9 and a newly identified crosslink repair protein, MUS312. Genetic analyses of mus312 mutants will be done to better understand which repair and recombination pathways require mus312, and to what extent mus312 and mei-9 act in the same pathways. Additional alleles of mus312 will be generated to better understand the MUS312 protein. Both mei-9 and mus312 are also essential for generating meiotic crossovers, and this function will also be studied genetically and molecularly.DNA is under constant attack by both internal and external agents; several chemotherapy agents exert their effects by creating interstrand crosslinks in DNA. The mechanisms by which normal cells repair this type of damage are unknown. The present research seeks to understand the contribution to this repair of two key proteins, MEI-9 and MUS312. These proteins interact physically to carry out this repair process in Drosophila melanogaster.
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