Cohesion is established during DNA replication utilising chromosome associated cohesin rings as well as those loaded de novo onto nascent DNAs

Srinivasan, Manoj; Fumasoni, Marco; Petela, Naomi J; Murray, Andrew W.; Nasmyth, Kim

doi:10.7554/elife.56611

Cited by 48 publications

(72 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This DSB however is not channeled to HR by the downstream modules of the FA/BRCA pathway and might remain unrepaired; when a cell reaches metaphase, the sites of these unrepaired DSBs can be visualized as chromatid breaks. Of note, the piece of broken chromatid usually remains adjacent to its chromosome due to the mitotic chromatin structure and the cohesin proteins that hold together the sister chromatids and prevent their separation until anaphase [ 44 ] ( Figure 3 c).…”

Section: Double Strand Breaks Are At the Center Of Chromosome Abermentioning

confidence: 99%

Chromosome Instability in Fanconi Anemia: From Breaks to Phenotypic Consequences

García-de-Teresa

Rodríguez

Frı́as

2020

Genes

View full text Add to dashboard Cite

Fanconi anemia (FA), a chromosomal instability syndrome, is caused by inherited pathogenic variants in any of 22 FANC genes, which cooperate in the FA/BRCA pathway. This pathway regulates the repair of DNA interstrand crosslinks (ICLs) through homologous recombination. In FA proper repair of ICLs is impaired and accumulation of toxic DNA double strand breaks occurs. To repair this type of DNA damage, FA cells activate alternative error-prone DNA repair pathways, which may lead to the formation of gross structural chromosome aberrations of which radial figures are the hallmark of FA, and their segregation during cell division are the origin of subsequent aberrations such as translocations, dicentrics and acentric fragments. The deficiency in DNA repair has pleiotropic consequences in the phenotype of patients with FA, including developmental alterations, bone marrow failure and an extreme risk to develop cancer. The mechanisms leading to the physical abnormalities during embryonic development have not been clearly elucidated, however FA has features of premature aging with chronic inflammation mediated by pro-inflammatory cytokines, which results in tissue attrition, selection of malignant clones and cancer onset. Moreover, chromosomal instability and cell death are not exclusive of the somatic compartment, they also affect germinal cells, as evidenced by the infertility observed in patients with FA.

show abstract

Section: Double Strand Breaks Are At the Center Of Chromosome Abermentioning

confidence: 99%

Chromosome Instability in Fanconi Anemia: From Breaks to Phenotypic Consequences

García-de-Teresa

Rodríguez

Frı́as

2020

Genes

View full text Add to dashboard Cite

show abstract

Section: Non-rejoined Structural Chromosomal Aberrations: Breaksmentioning

confidence: 99%

Chromosome Instability in Fanconi Anemia: From Breaks to Phenotypic Consequences

García-de-Teresa

Rodríguez

Frı́as

2020

Preprint

View full text Add to dashboard Cite

Fanconi anemia (FA), a chromosomal instability syndrome, is caused by inherited pathogenic variants in any of 22 FANC genes, that cooperate in the FA/BRCA pathway. This pathway regulates the repair of DNA interstrand crosslinks (ICLs) through homologous recombination. In FA proper repair of ICLs is impaired, and accumulation of toxic DNA double strand breaks occurs. In order to repair this type of DNA damage, FA cells activate alternative error-prone DNA repair pathways, that may lead to the formation of gross structural chromosome aberrations of which radial figures are the hallmark of FA and their segregation during cell division are the origin of subsequent aberrations like translocations, dicentrics and acentric fragments. The deficiency in DNA repair has pleiotropic consequences in the phenotype of patients with FA, including developmental alterations, bone marrow failure and an extreme risk to develop cancer. The mechanisms leading to the physical abnormalities during embryonic development have not been clearly elucidated, however FA has features of premature aging with chronic inflammation mediated by pro-inflammatory cytokines, that results in tissue attrition, selection of malignant clones and cancer onset. Moreover, the effect of the FA/BRCA pathway in germinal cells, evidenced by infertility in patients with FA attests of chromosomal instability and cell death also occurring in the germinal compartment.

show abstract

“…This DSB however is not channeled to HR by the downstream modules of the FA/BRCA pathway and might remain unrepaired; when a cell reaches metaphase, the sites of these unrepaired DSBs can be visualized as chromatid breaks. Of note, the piece of broken chromatid usually remains adjacent to its chromosome as a result of the structure of mitotic chromatin and cohesin proteins that hold together the sister chromatids and prevents their separation until anaphase [38] (Figure 3c).…”

Section: Breaksmentioning

confidence: 99%

Causes and Consequences of Chromosomal Instability in Fanconi Anemia. Alterations at the Cellular and Organism Level

García-de-Teresa¹,

Rodríguez²,

Frı́as³

2020

Preprint

View full text Add to dashboard Cite

Fanconi anemia (FA), a chromosome instability syndrome, is caused by inherited pathogenic variants in any of 22 FANC genes, that cooperate in the FA/BRCA pathway. This pathway regulates the repair of DNA interstrand crosslinks (ICLs) through homologous recombination. In FA proper repair of ICLs is impaired, and accumulation of toxic DNA double strand breaks occurs. In order to repair this type of DNA damage, FA cells activate alternative error-prone DNA repair pathways, that may lead to the formation of gross structural chromosome aberrations of which radial figures are the epitome and origin of subsequent aberrations like translocations, dicentrics and acentric fragments. The deficiency in DNA repair has pleiotropic consequences in the phenotype of patients with FA, including developmental alterations, bone marrow failure and an extreme risk to develop cancer. The mechanisms leading to the physical abnormalities during embryonic development have not been clearly elucidated, however FA has features of premature aging with chronic inflammation mediated by pro-inflammatory cytokines, that results in tissue attrition, selection of malignant clones and cancer onset. Moreover, the effect of the FA/BRCA pathway in germinal cells, evidenced by infertility in patients with FA attests of chromosomal instability and cell death also occurring in the germinal compartment.

show abstract

Cohesion is established during DNA replication utilising chromosome associated cohesin rings as well as those loaded de novo onto nascent DNAs

Cited by 48 publications

References 65 publications

Chromosome Instability in Fanconi Anemia: From Breaks to Phenotypic Consequences

Chromosome Instability in Fanconi Anemia: From Breaks to Phenotypic Consequences

Chromosome Instability in Fanconi Anemia: From Breaks to Phenotypic Consequences

Causes and Consequences of Chromosomal Instability in Fanconi Anemia. Alterations at the Cellular and Organism Level

Contact Info

Product

Resources

About