Control of Sister Chromatid Recombination by Histone H2AX

Xie, Anyong; Puget, Nadine; Shim, In‐Bo; Odate, Shobu; Jarzyna, Ingeborga; Bassing, Craig H.; Alt, Frederick W.; Scully, Ralph

doi:10.1016/j.molcel.2004.12.007

Cited by 194 publications

(234 citation statements)

References 39 publications

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“…DNA polymerase stalling lesion is indicated by a black square. The HR function of BRCA1 depicted here is independent of the H2AX response [48].…”

Section: When the Levee Breaks: Dsgs Genomic Instability And Cancermentioning

confidence: 74%

“…The eukaryotic chromosome is packaged into chromatin, which adds additional complexity to the control of all chromosomal processes, including recombination [45][46][47][48]. Unlike E. coli, eukaryotic chromosomes possess numerous potential origins of replication, of which only a fraction are used to initiate DNA synthesis in each cell cycle.…”

Section: Recombination-dependent Replication Restart In Eukaryotes: Amentioning

confidence: 99%

“…Phosphorylation of H2AX ("γ-H2AX") is a rapid, evolutionarily conserved event in the DSB response of eukaryotes and marks chromatin for hundreds of kilobases flanking the DSB [129]. H2AX contributes to DSBR, including SCR, by mechanisms that may involve cohesin complexes [46][47][48]130,131]. This "double life" of BRCA1 on ssDNA and on chromatin further underscores the diversity of functions of this protein, which include HR control, transcriptional regulation/gene silencing and DNA damage checkpoint control.…”

Section: Molecular Functions Of Brca1 and Brca2mentioning

confidence: 99%

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Minding the gap: The underground functions of BRCA1 and BRCA2 at stalled replication forks

Nagaraju

Scully

2007

DNA Repair

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The hereditary breast and ovarian cancer predisposition genes, BRCA1 and BRCA2, participate in the repair of DNA double strand breaks by homologous recombination. Circumstantial evidence implicates these genes in recombinational responses to DNA polymerase stalling during the S phase of the cell cycle. These responses play a key role in preventing genomic instability and cancer. Here, we review the current literature implicating the BRCA pathway in HR at stalled replication forks and explore the hypothesis that BRCA1 and BRCA2 participate in the recombinational resolution of single stranded DNA lesions termed "daughter strand gaps", generated during replication across a damaged DNA template.

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“…DNA polymerase stalling lesion is indicated by a black square. The HR function of BRCA1 depicted here is independent of the H2AX response [48].…”

Section: When the Levee Breaks: Dsgs Genomic Instability And Cancermentioning

confidence: 74%

Section: Recombination-dependent Replication Restart In Eukaryotes: Amentioning

confidence: 99%

Section: Molecular Functions Of Brca1 and Brca2mentioning

confidence: 99%

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Minding the gap: The underground functions of BRCA1 and BRCA2 at stalled replication forks

Nagaraju

Scully

2007

DNA Repair

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“…15,20,46,47 10 mg of each Ter/HR reporter ROSA26 targeting plasmid was linearized by Kpn I digest and introduced by electroporation to 2 £ 10 7 cells. Cells were seeded on plates prepared previously with puromycin-resistant feeders.…”

Section: Mouse Cell Lines and Cell Culturementioning

confidence: 99%

“…18,47 For all experiments, mouse ES cell clones harboring an intact copy of the reporter integrated at the ROSA26 locus on chromosome 6 were used. Genomic DNA was extracted from ES cells grown to confluency on gelatinized 6-well plates (»5-10 £ 10 6 cells) using a Puregene DNA Isolation Kit (Gentra Systems).…”

Section: Southern Blottingmentioning

confidence: 99%

Spatial separation of replisome arrest sites influences homologous recombination quality at a Tus/Ter-mediated replication fork barrier

Willis

Scully

2016

Cell Cycle

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The Escherichia coli replication fork arrest complex Tus/Ter mediates site-specific replication fork arrest and homologous recombination (HR) on a mammalian chromosome, inducing both conservative "short tract" gene conversion (STGC) and error-prone "long tract" gene conversion (LTGC) products. We showed previously that bidirectional fork arrest is required for the generation of STGC products at Tus/Ter-stalled replication forks and that the HR mediators BRCA1, BRCA2 and Rad51 mediate STGC but suppress LTGC at Tus/Ter-arrested forks. Here, we report the impact of Ter array length on Tus/Ter-induced HR, comparing HR reporters containing arrays of 6, 9, 15 or 21 Ter sites-each targeted to the ROSA26 locus of mouse embryonic stem (ES) cells. Increasing Ter copy number within the array beyond 6 did not affect the magnitude of Tus/Ter-induced HR but biased HR in favor of LTGC. A "lock"-defective Tus mutant, F140A, known to exhibit higher affinity than wild type (wt)Tus for duplex Ter, reproduced these effects. In contrast, increasing Ter copy number within the array reduced HR induced by the I-SceI homing endonuclease, but produced no consistent bias toward LTGC. Thus, the mechanisms governing HR at Tus/Ter-arrested replication forks are distinct from those governing HR at an enzyme-induced chromosomal double strand break (DSB). We propose that increased spatial separation of the 2 arrested forks encountering an extended Tus/Ter barrier impairs the coordination of DNA ends generated by the processing of the stalled forks, thereby favoring aberrant LTGC over conservative STGC.

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Sister Chromatid Cohesion, Chromosome Instability (CIN) and Diseases

Zhang

Yuen

2020

Encyclopedia of Life Sciences

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To pass on the complete set of genetic information from mother to daughter cells in mitosis, or from parental germ cells to gametes in meiosis, chromosomal deoxyribonucleic acid (DNA) must be accurately replicated and sister chromatids must be held together before they separate in anaphase. Sister chromatid cohesion is a dynamic process that is regulated by the cohesin complex, cell cycle regulation of cohesin ring loading, cohesion establishment, maintenance and dissolution. Cohesion‐related proteins also play additional roles in DNA replication, DNA repair, and gene regulation. Defects in sister chromatid cohesion or cohesion dissolution will lead to aneuploidy and chromosome instability (CIN). Mutations or misregulation of cohesin subunits, or cohesion‐related genes have been implicated in cancers, cohesinopathies, neurological diseases and aneuploid oocytes observed in maternal ageing. Understanding of the pathology of these diseases enables recent development of cohesion genes as biomarkers in prognosis and therapies that target cohesion defects or CIN. Key Concepts Sister chromatid cohesion is an important cell cycle‐regulated process that maintains chromosome stability. Sister chromatid cohesion is established in S phase coupled with DNA replication, maintained in G2/M phase until anaphase onset. Many cohesion‐related proteins also play roles in DNA replication, DNA repair and gene regulation. Mutations or misregulation of cohesin subunits, or cohesion‐related genes have been implicated in cancers, cohesinopathies, neurological diseases and aneuploid oocytes observed in maternal ageing. Cohesion genes can be used as biomarkers in cancer prognosis, and cancer therapies can target tumours with cohesion defects or CIN.

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Control of Sister Chromatid Recombination by Histone H2AX

Cited by 194 publications

References 39 publications

Minding the gap: The underground functions of BRCA1 and BRCA2 at stalled replication forks

Minding the gap: The underground functions of BRCA1 and BRCA2 at stalled replication forks

Spatial separation of replisome arrest sites influences homologous recombination quality at a Tus/Ter-mediated replication fork barrier

Sister Chromatid Cohesion, Chromosome Instability (CIN) and Diseases

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