Homolog-Dependent Repair Following Dicentric Chromosome Breakage in Drosophila melanogaster
Homolog-Dependent Repair Following Dicentric Chromosome Breakage in Drosophila melanogaster
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DOI：
10.1534/genetics.119.302247
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发表时间：
2019-07-01
期刊：
影响因子：
3.3
通讯作者：
Golic, Kent G.
中科院分区：
文献类型：
--
作者：
Bhandari, Jayaram;Karg, Travis;Golic, Kent G.
双链DNA断裂是通过几种机制中的一种来修复的，这种机制将断裂的两端重新连接起来。然而，当被要求修复单个断裂端时，细胞会受到挑战，并通过以下方式做出反应：(1)诱导程序性细胞死亡；(2)通过构建新的端粒修复断裂端；(3)适应断裂端，不经修复恢复有丝分裂周期；(4)利用姐妹染色单体或同源染色体的信息来恢复正常的染色体末端。在酵母中同源依赖性修复的一种形式中，称为断裂诱导复制（BIR），模板染色体可以复制数百个碱基。BIR的效率取决于Pif1解旋酶和Pol32 （DNA聚合酶δ的非必需亚基）。迄今为止，很少有证据表明BIR可以用于高等真核生物的广泛染色体修复。我们报道了黑腹果蝇雄性生殖系有丝分裂中双中心染色体断裂通常通过愈合修复，但也可以以同源依赖的方式修复，恢复至少1.3 Mb的末端序列信息。这种修复模式在pif1和pol32突变体中显著减少。正式地说，修复的染色体是重组体。然而，相互重组的缺失和对Pif1和Pol32的依赖有力地支持了BIR是染色体末端恢复机制的假设。与酵母相比，果蝇的pif1突变体表现出染色体愈合率降低，可能是由于这些生物体之间端粒的根本差异。
Double-strand DNA breaks are repaired by one of several mechanisms that rejoin two broken ends. However, cells are challenged when asked to repair a single broken end and respond by: (1) inducing programmed cell death; (2) healing the broken end by constructing a new telomere; (3) adapting to the broken end and resuming the mitotic cycle without repair; and (4) using information from the sister chromatid or homologous chromosome to restore a normal chromosome terminus. During one form of homolog-dependent repair in yeast, termed break-induced replication (BIR), a template chromosome can be copied for hundreds of kilobases. BIR efficiency depends on Pif1 helicase and Pol32, a nonessential subunit of DNA polymerase delta. To date, there is little evidence that BIR can be used for extensive chromosome repair in higher eukaryotes. We report that a dicentric chromosome broken in mitosis in the male germline of Drosophila melanogaster is usually repaired by healing, but can also be repaired in a homolog-dependent fashion, restoring at least 1.3 Mb of terminal sequence information. This mode of repair is significantly reduced in pif1 and pol32 mutants. Formally, the repaired chromosomes are recombinants. However, the absence of reciprocal recombinants and the dependence on Pif1 and Pol32 strongly support the hypothesis that BIR is the mechanism for restoration of the chromosome terminus. In contrast to yeast, pif1 mutants in Drosophila exhibit a reduced rate of chromosome healing, likely owing to fundamental differences in telomeres between these organisms.