Clusters of transcription-coupled repair in the human genome

Surrallés, Jordi; Ramı́rez, Marı́a José; Marcos, Ricard; Natarajan, A.T.; Mullenders, Leon H.F.

doi:10.1073/pnas.162278199

Cited by 33 publications

(25 citation statements)

References 30 publications

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“…early replicating gene-rich bands (Surralles et al 2002). We find a relatively strong pairwise correlation between germ-line expression and divergence (Supplemental Table 2), but no or only a weak association in our full model (Tables 1 and 2), which is most likely caused by higher error rates in the expression measures as compared to the sequence motifs.…”

Section: Discussion Predictors Of Mutation Ratesmentioning

confidence: 73%

“…At a larger scale, the comparison of mouse and human sequences has revealed that divergence correlates with GC and CpG content as well as with recombination rates (Mouse Genome Sequencing Consortium 2002; Hardison et al 2003). In addition, we would expect mutation rates to vary according to genomic features such as gene expression and the density of genes and repeats because these features are linked either directly or indirectly to the occurrence of DNA damage and/or repair mechanisms (Holmquist 1992;Surralles et al 2002).…”

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confidence: 99%

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Why do human diversity levels vary at a megabase scale?

Hellmann¹,

Prüfer²,

Zody³

et al. 2005

Genome Res.

158

181

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Levels of diversity vary across the human genome. This variation is caused by two forces: differences in mutation rates and the differential impact of natural selection. Pertinent to the question of the relative importance of these two forces is the observation that both diversity within species and interspecies divergence increase with recombination rates. This suggests that mutation and recombination are either directly coupled or linked through some third factor. Here, we test these possibilities using the recently generated sequence of the chimpanzee genome and new estimates of human diversity. We find that measures of GC and CpG content, simple-repeat structures, as well as the distance from the centromeres and the telomeres predict diversity as well as divergence. After controlling for these factors, large-scale recombination rates measured from pedigrees are still significant predictors of human diversity and human-chimpanzee divergence. Furthermore, the correlation between human diversity and recombination remains significant even after controlling for human-chimpanzee divergence. Two plausible and non-mutually exclusive explanations are, first, that natural selection has shaped the patterns of diversity seen in humans and, second, that recombination rates across the genome have changed since humans and chimpanzees shared a common ancestor, so that current recombination rates are a better predictor of diversity than of divergence. Because there are indications that recombination rates may have changed rapidly during human evolution, we favor the latter explanation.

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Section: Discussion Predictors Of Mutation Ratesmentioning

confidence: 73%

mentioning

confidence: 99%

Why do human diversity levels vary at a megabase scale?

Hellmann¹,

Prüfer²,

Zody³

et al. 2005

Genome Res.

158

181

View full text Add to dashboard Cite

show abstract

“…Chromatin structure affects DNA accessibility for a variety of nuclear processes including DNA repair and recombination (Surralles et al 2002;Gilbert et al 2004). Another observation is that genes regulated in cis tend to reside in genome regions (linkage disequilibrium blocks) that have been separated for longer evolutionary time and have accumulated structural changes.…”

Section: Discussionmentioning

confidence: 99%

Global Analysis of Allele-Specific Expression in Arabidopsis thaliana

2009

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Gene expression is a complex trait determined by various genetic and nongenetic factors. Among the genetic factors, allelic difference may play a critical role in gene regulation. In this study we globally dissected cis (allelic) and trans sources of genetic variation in F 1 hybrids between two Arabidopsis thaliana wild accessions, Columbia (Col) and Vancouver (Van), using a new high-density SNP-tiling array. This array tiles the whole genome with 35-bp resolution and interrogates 250,000 SNPs identified from resequencing of 20 diverse A. thaliana strains. Quantitative assessment of 12,311 genes identified 3811 genes differentially expressed between parents, 1665 genes with allele-specific expression, and 1688 genes controlled by composite trans-regulatory variation. Loci with cis-or trans-regulatory variation were mapped onto sequence polymorphisms, epigenetic modifications, and transcriptional specificity. Genes regulated in cis tend to be located in polymorphic chromosomal regions, are preferentially associated with repressive epigenetic marks, and exhibit high tissue expression specificity. Genes that vary due to trans regulation reside in relatively conserved chromosome regions, show activating epigenetic marks and generally constitutive gene expression. Our findings demonstrate a method of global functional characterization of allele-specific expression and highlight that chromatin structure is intertwined with evolution of cis-and trans-regulatory variation.

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“…Sp1 Depletion Renders Cells More Sensitive to DNA Damage GC-rich regions of the genome are unusually sensitive to DNA damage by alkylating agents and represent more open regions of chromatin (48)(49)(50)(51). Because Sp1 binds to GC boxes, we sought to determine the effect of Sp1 depletion on the induction of DSBs by ionizing radiation.…”

Section: The Atm Pathway Mediates the Phosphorylation Of Sp1mentioning

confidence: 99%

Phosphorylation of Sp1 in Response to DNA Damage by Ataxia Telangiectasia-Mutated Kinase

Olofsson

Kelly

Kim

et al. 2007

Molecular Cancer Research

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Sp1, a transcription factor that regulates expression of a wide array of essential genes, contains two SQ/TQ cluster domains, which are characteristic of ATM kinase substrates. ATM substrates are transducers and effectors of the DNA damage response, which involves sensing damage, checkpoint activation, DNA repair, and/or apoptosis. A role for Sp1 in the DNA damage response is supported by our findings: Activation of ATM induces Sp1 phosphorylation with kinetics similar to H2AX; inhibition of ATM activity blocks Sp1 phosphorylation; depletion of Sp1 sensitizes cells to DNA damage and increases the frequency of double strand breaks. We have identified serine 101 as a critical site phosphorylated by ATM; Sp1 with serine 101 mutated to alanine (S101A) is not significantly phosphorylated in response to damage and cannot restore increased sensitivity to DNA damage of cells depleted of Sp1. Together, these data show that Sp1 is a novel ATM substrate that plays a role in the cellular response to DNA damage. (Mol Cancer Res 2007;5(12):1319 -30)

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Clusters of transcription-coupled repair in the human genome

Cited by 33 publications

References 30 publications

Why do human diversity levels vary at a megabase scale?

Why do human diversity levels vary at a megabase scale?

Global Analysis of Allele-Specific Expression in Arabidopsis thaliana

Phosphorylation of Sp1 in Response to DNA Damage by Ataxia Telangiectasia-Mutated Kinase

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