분열효모 라머카이네이즈에 의한 DNA 복제 스트레스 반응 조절 = LAMMER kinase modulates the DNA replicative stress response in fission yeast

국문 초록 (Abstract)

본 연구에서는 분열효모 Schizosaccharomyces pombe의 라머카이네이즈(Lkh1) 결손 돌연변이주가 하이드록시유레아(HU) 등에 의해 유도되는 DNA 복제 체크포인트와의 연관성을 조사하였다. Lkh1-결손주는 특정 농도(5 mM) 이상의 HU 에 민감하였으며, DNA 복제 체크포인트의 센서카이네이즈인 Rad3-결손주는 Lkh1-결손주 보다 HU에 더 민감하였다. 한편, Lkh1과 Rad3가 모두 결손된 이중 돌연변이주는 Rad3 결손주와 동일한 수준의 HU 감수성을 보였으며, HU 처리로Lkh1-결손주의 rad3+ 및 하위 유전자 발현이 증가하였다. 이는 DNA 복제 체크포인트를 작동하는 Rad3의 활성이 Lkh1에의해 음성조절됨을 시사하는 것이다. 한편, Lkh1과 Rad3 사이에서 작용하는 전사조절인자를 규명하기 위하여 Lkh1 하위의조절자인 Tup11, Tup12 및 Prk1 결손주의 HU 민감성과 Rad3 유전자 발현을 조사한 결과, Tup11/Tup12 유전자가 동시에결실된 이중 돌연변이주만 HU 민감성을 보였으며 Rad3 유전자 발현도 감소하였다. 이러한 결과는 HU 처리에 의한 Rad3 유전자 발현조절에 Tup11과 Tup12가 동시에 관여하나 이들의 활성화 Lkh1가 아닌 미지의 조절자에 의해 이루어짐을 시사한다.

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