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CHROMATIN GEOMETRY AND INTRACHANGE PROXIMITY EFFECTS

染色质几何结构和变化内邻近效应

基本信息

批准号：
6180500
负责人：
RAINER K SACHS
金额：
$ 27.08万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-05-01 至 2002-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6180500
关键词：
DNA damage apoptosis cell cycle chromatin chromosome aberrations chromosome walking computer simulation conformation gene frequency genetic recombination mathematical model mutant polymers radiation dosage radiation genetics

项目摘要

DESCRIPTION: Although chromosomes are the largest and most important of all biomolecules, comparatively little is known about their large-scale geometric configurations and motions during cell cycle interphase. Radiation-produced chromosome aberrations, especially the rich variety of aberrations that can no be scored using fluorescent in situ hybridization techniques, are informative about chromosome structure during G0/G1, because the relative frequency of different aberration types is influenced by chromosome geometry and motion. Aberrations are also robustly implicated in all the medical aspects of radiobiology, including carcinogenesis, killing of cells in tumors or surrounding normal tissues, and retrospective biodosimetry. In particular, exchange-type, intrachromosomal, chromosome aberrations (chromosome interchanges, i.e., inversions and ring/deletion events) are important for all these reason, but are as yet less well understood, experimentally and theoretically, than are other aberration types. Intrachanges are important especially because they are formed much more frequently than randomness estimates based on genomic content would predict. The high frequency stems fro proximity effects, which enhance the probability of pairwise DSB illegitimate recombination if the two DSBs are initially formed close together, as they typically are if both DSBs are on the same chromosome. For example, inversions play a role in carcinogenesis similar to that of translocations, and they may be almost as frequent as translocations because there are so many small inversions; similarly, small deletions can be carcinogenic. The grant will undertake theoretical and computer calculations, relating proximity effects fo intrachanges at low or high LET to large-scale interphase chromatin geometry. Recent polymer models of large-scale chromatin conformation during G0/G1 will be extended to incorporate chromatin tethering and chromatin motion. The polymer models lead to predictions on the intrachange size spectrum; for example estimates on the frequency of intrachanges too small to be observed microscopically can be derived from the observed ratio of intra-arm to inter-arm intrachanges. Mechanistic computer and biophysical modeling is proposed as a comparatively inexpensive way to maximize information obtainable on chromatin geometry from the rapidly increasing database on aberrations, and to help guide experiments.

描述：虽然染色体是最大和最重要的

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Underprediction of visibly complex chromosome aberrations by a recombinational-repair ('one-hit') model.

重组修复（“一次性”）模型对明显复杂的染色体畸变的预测不足。

DOI：
10.1080/095530000138790
发表时间：
2000
期刊：
International journal of radiation biology
影响因子：
2.6
作者：
Sachs,RK;Rogoff,A;Chen,AM;Simpson,PJ;Savage,JR;Hahnfeldt,P;Hlatky,LR
通讯作者：
Hlatky,LR

Clustering of radiation-produced breaks along chromosomes: modelling the effects on chromosome aberrations.

辐射产生的沿染色体断裂的聚集：模拟对染色体畸变的影响。

DOI：
10.1080/095530099139999
发表时间：
1999
期刊：
International journal of radiation biology
影响因子：
2.6
作者：
Sachs,RK;Chen,AM;Simpson,PJ;Hlatky,LR;Hahnfeldt,P;Savage,JR
通讯作者：
Savage,JR

On target cell numbers in radiation-induced H4-RET mediated papillary thyroid cancer.

辐射诱导的 H4-RET 介导的乳头状甲状腺癌中的靶细胞数量。

DOI：
10.1007/s004110100108
发表时间：
2001
期刊：
Radiation and environmental biophysics
影响因子：
1.7
作者：
Radivoyevitch,T;Sachs,RK;Nikiforov,YE;Nikiforova,MN;Little,MP
通讯作者：
Little,MP

Random breakage and reunion chromosome aberration formation model; an interaction-distance version based on chromatin geometry.

随机断裂与团聚染色体畸变形成模型；

DOI：
10.1080/09553000050201064
发表时间：
2000
期刊：
International journal of radiation biology
影响因子：
2.6
作者：
Sachs,RK;Levy,D;Chen,AM;Simpson,PJ;Cornforth,MN;Ingerman,EA;Hahnfeldt,P;Hlatky,LR
通讯作者：
Hlatky,LR

Locations of radiation-produced DNA double strand breaks along chromosomes: a stochastic cluster process formalism.