DNA instability at chromosomal fragile sites in cancer.
DNA instability at chromosomal fragile sites in cancer.
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DOI：
10.2174/138920210791616699
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发表时间：
2010-08
期刊：
影响因子：
2.6
通讯作者：
Wang YH
中科院分区：
文献类型：
--
作者：
Dillon LW;Burrow AA;Wang YH
Human chromosomal fragile sites are specific genomic regions which exhibit gaps or breaks on metaphase chromosomes following conditions of partial replication stress. Fragile sites often coincide with genes that are frequently rearranged or deleted in human cancers, with over half of cancer-specific translocations containing breakpoints within fragile sites. But until recently, little direct evidence existed linking fragile site breakage to the formation of cancer-causing chromosomal aberrations. Studies have revealed that DNA breakage at fragile sites can induce formation of RET/PTC rearrangements, and deletions within the FHIT gene, resembling those observed in human tumors. These findings demonstrate the important role of fragile sites in cancer development, suggesting that a better understanding of the molecular basis of fragile site instability is crucial to insights in carcinogenesis. It is hypothesized that under conditions of replication stress, stable secondary structures form at fragile sites and stall replication fork progress, ultimately resulting in DNA breaks. A recent study examining an FRA16B fragment confirmed the formation of secondary structure and DNA polymerase stalling within this sequence in vitro, as well as reduced replication efficiency and increased instability in human cells. Polymerase stalling during synthesis of FRA16D has also been demonstrated. The ATR DNA damage checkpoint pathway plays a critical role in maintaining stability at fragile sites. Recent findings have confirmed binding of the ATR protein to three regions of FRA3B under conditions of mild replication stress. This review will discuss recent advances made in understanding the role and mechanism of fragile sites in cancer development.
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影响因子：
64.5
作者：
Casper, AM;Nghiem, P;Glover, TW
通讯作者：
Glover, TW
影响因子：
16
作者：
Coquelle, A;Toledo, F;Debatisse, M
通讯作者：
Debatisse, M
影响因子：
8
作者：
Durkin, S. G.;Arlt, M. F.;Glover, T. W.
通讯作者：
Glover, T. W.
影响因子：
21.3
作者：
Chan, Kok Lung;Palmai-Pallag, Timea;Hickson, Ian D.
通讯作者：
Hickson, Ian D.
DOI：
10.1158/1055-9965.epi-08-0960
发表时间：
2009-03
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Enewold L;Zhu K;Ron E;Marrogi AJ;Stojadinovic A;Peoples GE;Devesa SS
通讯作者：
Devesa SS