基因组护卫者与肿瘤抑止者

天狼星

基因组护卫者与肿瘤抑止者
科学家描述了小鼠的一个酶，这个酶与肿瘤的抑止和基因组的完整性都有关系。一个国际研究小组指出，人体中负责编码这种酶的基因应该是抑止因子的候选者。John Peter McPherson和同事报告说，拥有一个或两个受损的Mus81副本的小鼠，其淋巴癌和其它癌症的发病率都提高了，这些小鼠的染色体也更容易有自然的损伤，虽然这些小鼠能生存和由繁殖能力。因此，研究人员排除了Mus81酶在修复DNA程序性损伤或减数分裂重新组合中的作用。他们得出结论认为，基因组的完整性和肿瘤的抑止，需要Mus81双正常副本的表达。研究人员提出，当只有一个基因副本表达时，小鼠体内的Mus81蛋白质的量也许低于一个关键阈值。
报告：Involvement of Mammalian Mus81 in Genome Integrity and Tumor Suppression, John Peter McPherson, et al.

Involvement of Mammalian Mus81 in Genome Integrity and Tumor Suppression
John Peter McPherson,1,2* Bénédicte Lemmers,1,2 Richard Chahwan,1,2 Ashwin Pamidi,1,2 Eva Migon,1,2 Elzbieta Matysiak-Zablocki,1,2 Mary Ellen Moynahan,3 Jeroen Essers,4 Katsuhiro Hanada,4 Anuradha Poonepalli,5 Otto Sanchez-Sweatman,2 Rama Khokha,2 Roland Kanaar,4 Maria Jasin,3 M. Prakash Hande,5 Razqallah Hakem1,2

Mus81-Eme1 endonuclease has been implicated in the rescue of stalled replication forks and the resolution of meiotic recombination intermediates in yeast. We used gene targeting to study the physiological requirements of Mus81 in mammals. Mus81–/– mice are viable and fertile, which indicates that mammalian Mus81 is not essential for recombination processes associated with meiosis. Mus81-deficient mice and cells were hypersensitive to the DNA cross-linking agent mitomycin C but not to -irradiation. Remarkably, both homozygous Mus81–/– and heterozygous Mus81+/– mice exhibited a similar susceptibility to spontaneous chromosomal damage and a profound and equivalent predisposition to lymphomas and other cancers. These studies demonstrate a critical role for the proper biallelic expression of the mammalian Mus81 in the maintenance of genomic integrity and tumor suppression.

  Science, Vol 304, Issue 5678, 1822-1826 , 18 June 2004