The influence of DNA double-strand break structure on end-joining in human cells

Smith, Julianne; Baldeyron, Céline; Oliveira, Isabelle; Sala-Trepat, M.; Papadopoulo, Dora

doi:10.1093/nar/29.23.4783

Cited by 55 publications

(52 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Microhomologies may or may not be involved in the formation of the junction (66). Recently, there is evidence that error-free and error-prone end-joining have different genetic requirements (67), further supporting the idea that there is more than one pathway of NHEJ. Current evidence has supported the idea that BRCA1 is required for the error-free form of NHEJ (63,68), but the mechanism involved in this regulation of NHEJ is not known.…”

Section: Brca1 and Nhejmentioning

confidence: 97%

The Role of the BRCA1 Tumor Suppressor in DNA Double-Strand Break Repair

Zhang

Powell

2005

Molecular Cancer Research

187

154

View full text Add to dashboard Cite

The tumor suppressor gene BRCA1 was cloned in 1994 based on its linkage to early-onset breast and ovarian cancer. Although the BRCA1 protein has been implicated in multiple cellular functions, the precise mechanism that determines its tumor suppressor activity is not defined. Currently, the emerging picture is that BRCA1 plays an important role in maintaining genomic integrity by protecting cells from double-strand breaks (DSB) that arise during DNA replication or after DNA damage. The DSB repair pathways available in mammalian cells are homologous recombination and nonhomologous end-joining. BRCA1 function seems to be regulated by specific phosphorylations in response to DNA damage and we will focus this review on the roles played by BRCA1 in DNA repair and cell cycle checkpoints. Finally, we will explore the idea that tumor suppression by BRCA1 depends on its control of DNA DSB repair, resulting in the promotion of error-free and the inhibition of error-prone recombinational repair.

show abstract

Section: Brca1 and Nhejmentioning

confidence: 97%

The Role of the BRCA1 Tumor Suppressor in DNA Double-Strand Break Repair

Zhang

Powell

2005

Molecular Cancer Research

187

154

View full text Add to dashboard Cite

show abstract

“…HR is an efficient repair process that frequently results in gene and segmental duplication, gene loss, or inactivation. This contributes significantly to genome rearrangements and, thus, to genome instability (Gorbunova and Levy, 1997;Critchlow and Jackson, 1998;Kirik et al, 2000;Smith et al, 2001).…”

Section: Genome Stability Of the Exposed Plants: Study Of Homologous mentioning

confidence: 99%

Molecular Aspects of Plant Adaptation to Life in the Chernobyl Zone

et al. 2004

View full text Add to dashboard Cite

With each passing year since the Chernobyl accident of 1986, more questions arise about the potential for organisms to adapt to radiation exposure. Often this is thought to be attributed to somatic and germline mutation rates in various organisms. We analyzed the adaptability of native Arabidopsis plants collected from areas with different levels of contamination around the Chernobyl nuclear power plant from 1986 to 1992. Notably, progeny of Chernobyl plants resisted higher concentrations of the mutagens Rose Bengal and methyl methane sulfonate. We analyzed the possible molecular mechanisms of their resistance to mutagens and found a more than 10-fold lower frequency of extrachromosomal homologous recombination, significant differences in the expression of radical scavenging (CAT1 and FSD3) and DNA-repair (RAD1 and RAD51-like) genes upon exposure to mutagens (Rose Bengal and x-rays), and a higher level of global genome methylation. This data suggests that adaptation to ionizing radiation is a complex process involving epigenetic regulation of gene expression and genome stabilization that improves plants' resistance to environmental mutagens.

show abstract

“…At seven other junctions (37%), DNAs were directly joined (Figure 2b) or joined with insertion of several nucleotides (Figure 2c). The joining at these seven junctions was also likely to be undertaken by NHEJ, since NHEJ is also undertaken without utilizing a terminal microhomology and sometimes accompanied with insertion of extra nucleotides (Roth and Wilson, 1986;Smith et al, 2001). This result was unexpected.…”

mentioning

confidence: 99%

Molecular processes of chromosome 9p21 deletions in human cancers

Sasaki¹,

Kitagawa

Sekido

et al. 2003

Oncogene

View full text Add to dashboard Cite

Interstitial deletions of the chromosome 9p21 segment encoding the p16/CDKN2A tumor suppressor gene (i.e., 9p21 deletions) are frequently observed in a variety of human cancers. A majority of these deletions in lymphoid leukemia have been indicated to be mediated by illegitimate V(D)J recombination. In the present study, to elucidate the molecular processes of 9p21 deletions in nonlymphocytic malignancies, breakpoints for these deletions were analysed in 21 lung cancer cell lines and 32 nonlymphocytic cancer cell lines of nine other histological types. In all, 32 breakpoints in 21 lung cancer cell lines and 56 breakpoints in 32 nonlung cancer cell lines were mapped in a 450-kb segment encompassing the CDKN2A locus with a 10-kb resolution. The largest number of breakpoints (i.e., seven breakpoints in lung cancer and 12 breakpoints in nonlung cancers) was mapped in a 10-kb region containing the CDKN2A gene. More precise mapping of these seven and 12 breakpoints revealed that none of these breakpoints were located within 50-bp intervals to each other in this 10 kb region. Cloning and sequencing of breakpoints in 18 representative cell lines (six lung and 12 nonlung cancers) further revealed that there were no significant homologies among breakpoints in these 18 cell lines. In 11 (61%) cell lines, 1-5-bp nucleotides were overlapped at breakpoint junctions. These results indicate that DNA double-strand breaks triggering 9p21 deletions do not occur at specific DNA sequences, although they preferentially occur in or near the CDKN2A locus. It was also indicated that two broken DNA ends are rejoined by nonhomologous end-joining repair, preferentially utilizing microhomologies of DNA ends, in the occurrence of 9p21 deletions. Oncogene (2003) 22, 3792-3798. doi:10.1038/sj.onc.1206589Keywords: 9p21 deletion; p16/CDKN2A; lung cancer; DNA double-strand break; nonhomologous end joining Chromosome 9p deletions frequently occur in a variety of human cancers including lymphoid leukemia, lung cancer, esophageal cancer, glioma and melanoma, and the 9p21 segment including the p16/CDKN2A, p14/ARF and p15/CDKN2B loci has been defined as a common region for the deletions (Kamb et al., 1994;Nobori et al., 1994;Ohnishi et al., 1995;Tanaka et al., 1997;Drexler, 1998;Hamada et al., 1998Hamada et al., , 2000Park et al., 2002). The CDKN2A tumor suppressor gene and two other related genes, ARF and CDKN2B, encode critical regulators of cell cycle and/or apoptosis (Sherr, 2000). Thus, deletion of the 9p21 segment is a causative generic alteration inactivating the CDKN2A, ARF and/or CDKN2B genes, and is thought to play an important role in the development and/or progression of human cancers. Elucidation of the mechanism(s) for the deletions of the 9p21 segment is, therefore, indispensable in understanding the molecular pathways of multistage human carcinogenesis.Structural analyses of breakpoints for interstitial deletions of the 9p21 segment (i.e., 9p21 deletions) have been performed in lymphoid leukemia to predict the molecular processes of th...

show abstract

The influence of DNA double-strand break structure on end-joining in human cells

Cited by 55 publications

References 33 publications

The Role of the BRCA1 Tumor Suppressor in DNA Double-Strand Break Repair

The Role of the BRCA1 Tumor Suppressor in DNA Double-Strand Break Repair

Molecular Aspects of Plant Adaptation to Life in the Chernobyl Zone

Molecular processes of chromosome 9p21 deletions in human cancers

Contact Info

Product

Resources

About