CHROMATIN GEOMETRY AND INTRACHANGE PROXIMITY EFFECTS
CHROMATIN GEOMETRY AND INTRACHANGE PROXIMITY EFFECTS
批准号:
6180500
负责人:
RAINER K SACHS
金额:
$27.08万
依托单位国家:
美国
项目类别:
财政年份:
1998
资助国家:
美国
项目状态:
已结题
起止时间:
1998-05-01 至 2002-04-30
中文摘要
描述:虽然染色体是最大和最重要的所有
生物分子,相对而言,对它们的大规模
细胞周期间期的几何构型和运动。
辐射引起的染色体畸变,特别是各种各样的
不能用荧光原位杂交评分的畸变
技术,是关于染色体结构在G 0/G1,因为
不同像差类型的相对频率受
染色体的几何形状和运动。 畸变也强烈地涉及到
放射生物学的所有医学方面,包括致癌作用,
肿瘤或周围正常组织中的细胞,
生物剂量学 特别是交换型染色体内染色体
畸变(染色体互换,即,倒位和环/缺失
事件)对于所有这些原因都是重要的,但还没有那么好
在实验上和理论上,
类型 内变是很重要的,特别是因为它们的形成
比基于基因组内容的随机性估计更频繁,
预测。 高频源于邻近效应,这增强了
如果两个DSB是
最初形成时靠得很近,如果两个DSB都打开,
相同的染色体。 例如,倒位在致癌作用中起作用
类似于易位,它们可能几乎和
易位,因为有这么多的小倒位;同样,小
缺失可能是致癌的。 该赠款将承担理论和
计算机计算,在低或
高LET到大规模间期染色质几何学。 新聚合物
G 0/G1期大尺度染色质构象的模型将得到扩展
以结合染色质束缚和染色质运动。 聚合物模型
导致对变化内大小谱的预测;例如估计
在太小而不能在显微镜下观察到的内部变化的频率上
可以从观察到的组内与组间的比值中得出
内部变化。 提出了机械计算机和生物物理建模,
一种相对便宜的方法,以最大限度地提高信息可获得的
来自畸变数据库的快速增长的染色质几何形状,以及
来指导实验
英文摘要
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.
期刊论文(12)
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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
Computer analysis of mFISH chromosome aberration data uncovers an excess of very complicated metaphases.
mFISH 染色体畸变数据的计算机分析揭示了过多的非常复杂的中期。
DOI:
10.1080/09553000210166354
发表时间:
2002
期刊:
International journal of radiation biology.
影响因子:
--
作者:
[Vazquez,M, Greulich-Bode,KM, Arsuaga,J, Cornforth,MN, Bruckner,M, Sachs,RK, Hlatky,L, Molls,M, Hahnfeldt,P]
通讯作者:
Hahnfeldt,P
共 9 条
Project 5 UC Berkley
-
批准号:8181949
-
项目类别:
-
资助金额:$19.67万
-
财政年份:2010
-
负责人:RAINER K SACHS
-
依托单位:
Updating Chromosome Aberration Simulator (CAS) Software
-
批准号:7071703
-
项目类别:
-
资助金额:$18.96万
-
财政年份:2003
-
负责人:RAINER K SACHS
-
依托单位:
Updating Chromosome Aberration Simulator (CAS) Software
-
批准号:6901118
-
项目类别:
-
资助金额:$19.42万
-
财政年份:2003
-
负责人:RAINER K SACHS
-
依托单位:
Updating Chromosome Aberration Simulator (CAS) Software
-
批准号:6773956
-
项目类别:
-
资助金额:$19.42万
-
财政年份:2003
-
负责人:RAINER K SACHS
-
依托单位:
Updating Chromosome Aberration Simulator (CAS) Software
-
批准号:6668099
-
项目类别:
-
资助金额:$20.72万
-
财政年份:2003
-
负责人:RAINER K SACHS
-
依托单位:
CYTOGENETIC MODELS FOR ASSESSING LOW DOSE RADIATION RISK
-
批准号:6129500
-
项目类别:
-
资助金额:$21.54万
-
财政年份:1999
-
负责人:RAINER K SACHS
-
依托单位:
CYTOGENETIC MODELS FOR ASSESSING LOW DOSE RADIATION RISK
-
批准号:6377956
-
项目类别:
-
资助金额:$21.66万
-
财政年份:1999
-
负责人:RAINER K SACHS
-
依托单位:
CYTOGENETIC MODELS FOR ASSESSING LOW DOSE RADIATION RISK
-
批准号:6175032
-
项目类别:
-
资助金额:$21.97万
-
财政年份:1999
-
负责人:RAINER K SACHS
-
依托单位:
CHROMATIN GEOMETRY AND INTRACHANGE PROXIMITY EFFECTS
-
批准号:2910389
-
项目类别:
-
资助金额:$16.9万
-
财政年份:1998
-
负责人:RAINER K SACHS
-
依托单位:
POLYMER CHROMATIN MODELS OF DOUBLE-STRAND-BREAK CLUSTERS
-
批准号:2900919
-
项目类别:
-
资助金额:$7.35万
-
财政年份:1998
-
负责人:RAINER K SACHS
-
依托单位:
CHROMATIN GEOMETRY AND INTRACHANGE PROXIMITY EFFECTS
-
批准号:2562609
-
项目类别:
-
资助金额:$17.44万
-
财政年份:1998
-
负责人:RAINER K SACHS
-
依托单位:
SOFTWARE TO COMPENSATE FOR INTERRUPTIONS IN RADIOTHERAPY
-
批准号:2106039
-
项目类别:
-
资助金额:$37.42万
-
财政年份:1994
-
负责人:RAINER K SACHS
-
依托单位:
SOFTWARE TO COMPENSATE FOR INTERRUPTIONS IN RADIOTHERAPY
-
批准号:2106038
-
项目类别:
-
资助金额:$7.5万
-
财政年份:1994
-
负责人:RAINER K SACHS
-
依托单位:
SOFTWARE TO COMPENSATE FOR INTERRUPTIONS IN RADIOTHERAPY
-
批准号:2106040
-
项目类别:
-
资助金额:$37.58万
-
财政年份:1994
-
负责人:RAINER K SACHS
-
依托单位:
Project 5 UC Berkley
-
批准号:8378773
-
项目类别:
-
资助金额:$16.32万
-
财政年份:--
-
负责人:RAINER K SACHS
-
依托单位:
Project 5 UC Berkley
-
批准号:8639494
-
项目类别:
-
资助金额:$15.69万
-
财政年份:--
-
负责人:RAINER K SACHS
-
依托单位:
Project 5 UC Berkley
-
批准号:8536741
-
项目类别:
-
资助金额:$15.35万
-
财政年份:--
-
负责人:RAINER K SACHS
-
依托单位:
Project 5 UC Berkley
-
批准号:8252185
-
项目类别:
-
资助金额:$20.68万
-
财政年份:--
-
负责人:RAINER K SACHS
-
依托单位:
国内基金
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批准年份:1995
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负责人:梁克
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