Functional relation among RecQ family Helicases RecQL1, RecQL5, and BLM in cell growth and sister chromatid exchange formation
Functional relation among RecQ family Helicases RecQL1, RecQL5, and BLM in cell growth and sister chromatid exchange formation
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DOI：
10.1128/mcb.23.10.3527-3535.2003
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发表时间：
2003-05-01
影响因子：
5.3
通讯作者：
Enomoto, T
中科院分区：
文献类型：
--
作者：
Wang, WS;Seki, M;Enomoto, T
人类 RECQL1 和 RECQL5 属于 RecQ 家族，该家族包括 Bloom 综合征、Werner 综合征和 Rothmund-Thomson 综合征致病基因。来自患有这些综合征的个体的细胞表现出显着水平的基因组不稳定性。然而，RECQL1和RECQL5都与疾病无关，并且对于RecQL1和RecQL5的功能一无所知。我们从鸡 B 淋巴细胞系 DT40 细胞中生成了 RECQL1(-/-)、RECQL5(-/-)、RECQL1(-/-)/RECQL5(-/-)、RECQL1(-/-)/BLM-/- 和 RECQL5(-/-)/BLM-/- 细胞。尽管BLM-/- DT40细胞表现出生长缓慢的表型，对甲磺酸甲酯的敏感性比野生型细胞更高，姐妹染色单体交换（SCE）频率比野生型细胞增加10倍，但PECQL1（-/-）、PECQL5（-/-）和RECQL1（-/-）/RECQL5（-/-）细胞没有表现出显着差异。 野生型细胞的生长、对 DNA 损伤剂的敏感性以及 SCE 的频率。然而，由于死细胞数量的增加，PECQL1(-/-)/BLM-/-和RECQL5(-/-)/BLM-/-细胞的生长速度比BLM-/-细胞更慢，表明RecQL1和RecQL5在BLM功能受损条件下以某种方式参与细胞活力。令人惊讶的是，PECQL5(-/-)/BLM-/-细胞比BLM-/-细胞表现出更高的SCE频率，表明RecQL5在BLM功能受损的条件下抑制SCE。
Human RECQL1 and RECQL5 belong to the RecQ family that includes Bloom syndrome, Werner syndrome, and Rothmund-Thomson syndrome causative genes. Cells derived from individuals suffering from these syndromes show significant levels of genomic instability. However, neither RECQL1 nor RECQL5 has been related to a disease, and nothing is known about the functions of RecQL1 and RecQL5. We generated here RECQL1(-/-), RECQL5(-/-), RECQL1(-/-)/RECQL5(-/-), RECQL1(-/-)/BLM-/-, and RECQL5(-/-)/BLM-/- cells from chicken B-lymphocyte line DT40 cells. Although BLM-/- DT40 cells showed a slow-growth phenotype, a higher sensitivity to methyl methanesulfonate than the wild type, and an similar to10-fold increase in the frequency of sister chromatid exchange (SCE) compared to wild-type cells, PECQL1(-/-), PECQL5(-/-), and RECQL1(-/-)/RECQL5(-/-) cells showed no significant difference from the wild-type cells in growth, sensitivity to DNA-damaging agents, and the frequency of SCE. However, both PECQL1(-/-)/BLM-/- and RECQL5(-/-)/BLM-/- cells grew more slowly than BLM-/- cells because of the increase in the population of dead cells, indicating that RecQL1 and RecQL5 are somehow involved in cell viability under the BLM function-impaired condition. Surprisingly, PECQL5(-/-)/BLM-/- cells showed a higher frequency of SCE than BLM-/- cells, indicating that RecQL5 suppresses SCE under the BLM function-impaired condition.