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Mối quan hệ giữa điều hòa canxi liên quan đến lưới nội chất và Golgi với sửa chữa DNA do 4-NQO gây ra trong Saccharomyces cerevisiae
Tóm tắt
Ion canxi (Ca2+) là một ion quan trọng cần thiết cho việc kích hoạt các cơ chế sửa chữa DNA khác nhau. Tuy nhiên, cơ chế mà qua đó sửa chữa DNA và cân bằng Ca2+ hợp tác vẫn chưa được làm sáng tỏ. Chúng tôi đã thực hiện một cách tiếp cận sinh học hệ thống để xác minh mối quan hệ giữa các protein liên quan đến cân bằng Ca2+ và sửa chữa DNA trong Saccharomyces cerevisiae. Dữ liệu của chúng tôi chỉ ra rằng Pmr1p, một chất vận chuyển Ca2+ của phức hợp Golgi, tương tác với Cod1p, protein điều chỉnh mức độ Ca2+ trong lưới nội chất (ER), và với Rad4p, một protein sửa chữa cắt bỏ nucleotide (NER). Thông tin này đã được sử dụng để xây dựng các đột biến đơn và kép thiếu hụt cho Pmr1p, Cod1p và Rad4p, tiếp theo là phân tích tác động độc tế bào, tác động tĩnh tế bào và sự ngưng trệ chu kỳ tế bào sau khi tế bào tiếp xúc với các nồng độ khác nhau của 4-nitroquinoline 1-oxide (4-NQO). Kết quả chỉ ra rằng các chủng cod1Δ, cod1Δrad4Δ và cod1Δpmr1Δ có độ nhạy cao hơn với 4-NQO so với chủng hoang dã (WT) của nó. Hơn nữa, cả hai chủng cod1Δpmr1Δ và cod1Δrad4Δ đều có sự ngưng trệ mạnh mẽ ở các pha G2/M của chu kỳ tế bào sau điều trị bằng 4-NQO, trong khi pmr1Δrad4Δ có độ nhạy và hồ sơ ngưng trệ chu kỳ tế bào tương tự khi so với rad4Δ sau khi tiếp xúc với 4-NQO. Tổng hợp lại, kết quả của chúng tôi cho thấy rằng sự thiếu hụt các chất vận chuyển Ca2+ liên quan đến Golgi và ER ảnh hưởng đến việc sửa chữa tổn thương DNA do 4-NQO gây ra.
Từ khóa
#canxi #sửa chữa DNA #Saccharomyces cerevisiae #Golgi #lưới nội chất #4-NQOTài liệu tham khảo
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