Rad52 function prevents chromosome loss and truncation in Candida albicans.
Rad52 function prevents chromosome loss and truncation in Candida albicans.
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DOI：
10.1111/j.1365-2958.2011.07532.x
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发表时间：
2011-03
影响因子：
3.6
通讯作者：
Larriba G
中科院分区：
文献类型：
--
作者：
Andaluz E;Bellido A;Gómez-Raja J;Selmecki A;Bouchonville K;Calderone R;Berman J;Larriba G
酿酒酵母中几乎所有的重组事件都需要RAD52。我们利用HIS4在白念珠菌SC5314谱系中的杂合性，研究了Rad52在这种重要的真菌病原菌基因组稳定性中的作用。RAD52-ΔΔ株HIS4的杂合性缺失(LOH)率约为10−3，至少是RAD52+株的100倍。在6个独立实验中获得的80个RAD52-ΔΔHis营养缺陷症细胞(GLH-GL Lab His−)中，均检测到完整的4号染色体LOH或携带HIS4功能等位基因的同源基因被截断。发生了整个染色体缺失的分离株，可能是由于染色体丢失，携带了剩余同源基因的两个副本。截断的分离株携带断裂的染色体的中心片段，通过重新添加端粒修复。GLH菌株在整个基因组中表现出不同程度的杂合性缺失，其中包括两个在所有杂合标记测试中变得纯合的菌株。此外，GLH菌株表现出更高的染色体不稳定性(CIN)，这一点可通过重新导入RAD52来消除。GLH分离株的CIN使人联想到导致人类细胞癌症的基因组变化，并支持突变子假说，即突变子突变或CIN表型有助于更多的突变/非整倍体。
RAD52 is required for almost all recombination events in S. cerevisiae. We took advantage of the heterozygosity of HIS4 in the C. albicans SC5314 lineage to study the role of Rad52 in the genomic stability of this important fungal pathogen. The rate of loss of heterozygosity (LOH) at HIS4 in rad52-ΔΔ strains was ~10−3, at least 100-fold higher than in Rad52+ strains. LOH of whole chromosome 4 or truncation of the homologue that carries the functional HIS4 allele was detected in all 80 rad52-ΔΔ His auxotrophs (GLH –GL lab His−) obtained from six independent experiments. Isolates that had undergone whole chromosome LOH, presumably due to loss of chromosome, carried two copies of the remaining homolog. Isolates with truncations carried centric fragments of broken chromosomes healed by de novo telomere addition. GLH strains exhibited variable degrees of LOH across the genome, including two strains that became homozygous for all the heterozygous markers tested. In addition, GLH strains exhibited increased chromosomal instability (CIN), which was abolished by reintroduction of RAD52. CIN of GLH isolates is reminiscent of genomic alterations leading to cancer in human cells, and support the mutator hypothesis in which a mutator mutation or CIN phenotype facilitate more mutations/aneuploidies.
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影响因子：
3.2
作者：
CHU, WS;MAGEE, BB;MAGEE, PT
通讯作者：
MAGEE, PT
影响因子：
3
作者：
Garcia-Prieto, Fatima;Gomez-Raja, Jonathan;Andaluz, Encarnacion;Calderone, Richard;Larriba, German
通讯作者：
Larriba, German
影响因子：
9.8
作者：
Forche A;Alby K;Schaefer D;Johnson AD;Berman J;Bennett RJ
通讯作者：
Bennett RJ
影响因子：
3.3
作者：
Forche, Anja;Magee, P. T.;May, Georgiana
通讯作者：
May, Georgiana
影响因子：
11.4
作者：
Bennett, RJ;Johnson, AD
通讯作者：
Johnson, AD