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조회 6178  인쇄하기 주소복사 트위터 공유 페이스북 공유 
Genome-wide profiles of H2AX and γ-H2AX differentiate endogenous and exogenous DNA damage hotspots in human cells

Jungmin Seo1, Sang Cheol Kim2, Heun-Sik Lee1, Jung Kyu Kim1, Hye Jin Shon3, Nur Lina Mohd Salleh4, Kartiki Vasant Desai4, Jae Ho Lee5, Eun-Suk Kang3, Jin Sung Kim6,* and Jung Kyoon Choi4,7,*

1Research Institute of Bioinformatics, Omicsis, Inc., BVC, KRIBB, Daejeon 305-333, Korea, 2Korean Bioinformation Center, KRIBB, Daejeon 305-333, Korea, 3Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea, 4Genome Institute of Singapore, Singapore 138672, Republic of Singapore, 5Laboratory of Molecular Oncology, Cheil General Hospital & Women’s Healthcare Center, Kwandong University College of Medicine, Seoul 100-380, Korea, 6Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea and 7Department of Bio and Brain Engineering, KAIST, Daejeon 305-701, Korea

*To whom correspondence should be addressed

Correspondence may also be addressed to Jin Sung Kim.

Abstract
Phosphorylation of the histone variant H2AX forms γ-H2AX that marks DNA double-strand break (DSB). Here, we generated the sequencing-based maps of H2AX and γ-H2AX positioning in resting and proliferating cells before and after ionizing irradiation. Genome-wide locations of possible endogenous and exogenous DSBs were identified based on γ-H2AX distribution in dividing cancer cells without irradiation and that in resting cells upon irradiation, respectively. γ-H2AX-enriched regions of endogenous origin in replicating cells included sub-telomeres and active transcription start sites, apparently reflecting replication- and transcription-mediated stress during rapid cell division. Surprisingly, H2AX itself, prior to phosphorylation, was specifically located at these endogenous hotspots. This phenomenon was only observed in dividing cancer cells but not in resting cells. Endogenous H2AX was concentrated on the transcription start site of actively transcribed genes but was irrelevant to pausing of RNA polymerase II (pol II), which precisely coincided with γ-H2AX of endogenous origin. γ-H2AX enrichment upon irradiation also coincided with actively transcribed regions, but unlike endogenous γ-H2AX, it extended into the gene body and was not specifically concentrated on the pausing site of pol II. Sub-telomeres were less responsive to external DNA damage than to endogenous stress. Our findings provide insight into DNA repair programs of cancer and may have implications for cancer therapy.

논문정보 F1000선정
- 형식: Research article
- 게재일: 2012년 03월 (BRIC 등록일 2012-07-09)
- 연구진: 국내(교신)+국외 연구진태극기
- 분야: Biochemistry, Molecular_Biology
- 추천: Faculty of 1000 Biology
- 추천사유: Faculty of 1000 evaluations, dissents and comments for [Seo J et al. Genome-wide profiles of H2AX and γ-H2AX differentiate endogenous and exogenous DNA damage hotspots in human cells. Nucleic Acids Res. 2012 Mar 29; doi: 10.1093/nar/gks287]. Faculty of 1000, . F1000.com/717697806
관련 인터뷰
1. 논문관련 분야의 소개, 동향, 전망을 설명, 연구과정에서 생긴 에피소드 세포에 방사선 조사시에 Double strand break와 같은 DNA damage가 일어나며, 히스톤 단백질 중 하나인 phosphorylated histone variant H2AX(γ-H2AX)에 대한 연구는 많이 있었으나 genome-wide study는 드물었습니다. 본 논문에서는 인간 유래 T cell과 암세포주를 이용하여 방사선 전후에 히스톤 단백질 중 하나인 H2AX와...
Dot/Icm 제 4 유형 커플링 단백질 복합체의 선택적 이펙터 단백질 인식[Nat. Commun.]
김현민
발표: 김현민 (KAIST)
일자: 2020년 9월 29일 (화) 오후 02시 (한국시간)
언어: 한국어
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  댓글 4
회원작성글 kimsc77  (2012-08-16 17:46)
ㅊㄱㅊㄱ
회원작성글 반효정  (2012-08-17 10:31)
축하해요~!!!
회원작성글 김미랑  (2012-08-17 15:18)
박사님, F1000 축하 드려요. 저도 논문 자세히 읽어봐야겠네요.
회원작성글 기므기  (2012-09-15 15:50)
오~~ 서정민 박사님. 늦었지만 축하드립니다.
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