DNA damage response proteins regulating mitotic cell division: double agents preserving genome stability

Petsalaki, Eleni; Zachos, George

doi:10.1111/febs.15240

Cited by 56 publications

(41 citation statements)

References 159 publications

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“…It has been shown that DNA repair factors can be recruited to mitotic spindles [145,152,153] or the main microtubule organizing centers, the centrosomes [145,[154][155][156][157][158][159]. However, it remains difficult to determine whether the presence of these proteins in mitosis has an actual role in regulating microtubule stability, as experiments using protein depletion make it complicated to discern the role of these proteins in interphase and mitosis.…”

Section: Replication Stress and Spindle Microtubulesmentioning

confidence: 99%

DNA Replication Stress and Chromosomal Instability: Dangerous Liaisons

Wilhelm

Said

Naim

2020

Genes

104

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Chromosomal instability (CIN) is associated with many human diseases, including neurodevelopmental or neurodegenerative conditions, age-related disorders and cancer, and is a key driver for disease initiation and progression. A major source of structural chromosome instability (s-CIN) leading to structural chromosome aberrations is “replication stress”, a condition in which stalled or slowly progressing replication forks interfere with timely and error-free completion of the S phase. On the other hand, mitotic errors that result in chromosome mis-segregation are the cause of numerical chromosome instability (n-CIN) and aneuploidy. In this review, we will discuss recent evidence showing that these two forms of chromosomal instability can be mechanistically interlinked. We first summarize how replication stress causes structural and numerical CIN, focusing on mechanisms such as mitotic rescue of replication stress (MRRS) and centriole disengagement, which prevent or contribute to specific types of structural chromosome aberrations and segregation errors. We describe the main outcomes of segregation errors and how micronucleation and aneuploidy can be the key stimuli promoting inflammation, senescence, or chromothripsis. At the end, we discuss how CIN can reduce cellular fitness and may behave as an anticancer barrier in noncancerous cells or precancerous lesions, whereas it fuels genomic instability in the context of cancer, and how our current knowledge may be exploited for developing cancer therapies.

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Section: Replication Stress and Spindle Microtubulesmentioning

confidence: 99%

DNA Replication Stress and Chromosomal Instability: Dangerous Liaisons

Wilhelm

Said

Naim

2020

Genes

104

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“…It is now becoming clear that abscission is a very complex and highly regulated event ( Schiel and Prekeris, 2010 ; Addi et al, 2018 ; Fremont and Echard, 2018 ). Indeed, recent studies identified a new mitotic checkpoint, known as abscission checkpoint, that is activated by lagging chromosomes and leads to the arrest of the cells in telophase ( Sadler et al, 2018 ; Bai et al, 2020 ; Petsalaki and Zachos, 2020 ). We now know that abscission involves highly organized remodeling of the cytoskeleton at the ICB.…”

Section: Discussionmentioning

confidence: 99%

Rab14/MACF2 complex regulates endosomal targeting during cytokinesis

Gibieža

Peterman

Hoffman

et al. 2021

MBoC

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Abscission is a complex cellular process that is required for mitotic division. It is well-established that coordinated and localized changes in actin and microtubule dynamics are vital for cytokinetic ring formation, as well as establishment of the abscission site. Actin cytoskeleton reorganization during abscission would not be possible without the interplay between Rab11- and Rab35-containing endosomes and their effector proteins, whose roles in regulating endocytic pathways at the cleavage furrow have now been studied extensively. Here, we identified Rab14 as a novel regulator of cytokinesis. We demonstrate that depletion of Rab14 causes either cytokinesis failure or significantly prolongs division time. We show that Rab14 contributes to the efficiency of recruiting Rab11-endosomes to the ICB microtubules and that Rab14 knockout leads to inhibition of actin clearance at the abscission site. Finally, we demonstrate that Rab14 binds to microtubule minus-end interacting MACF2/CAMSAP3 complex and that this binding affects targeting of endosomes to the ICB microtubules. Collectively, our data identified Rab14 and MACF2/CAMSAP3 as proteins that regulate actin depolymerization and endosome targeting during cytokinesis. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text]

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“…It is now becoming clear that abscission is a very complex and highly regulated event (Addi et al, 2018;Fremont and Echard 2018;Schiel and Prekeris 2010). Indeed, recent studies identified a new mitotic checkpoint, known as abscission checkpoint (also sometimes referred to as NoCut), that is activated by lagging chromosomes and leads to the arrest of the cells in telophase (Bai et al, 2020;Petsalaki and Zachos 2020;Sadler et al, 2018). We now know that abscission involves highly organized remodelling of the cytoskeleton at the ICB.…”

Section: Discussionmentioning

confidence: 99%

Rab14/MACF2/CAMSAP3 Complex Regulates Endosomal Targeting to the Abscission Site During Cytokinesis

Prekeris

Gibieža

Peterman

et al. 2020

Preprint

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Abscission is complex cellular process that is required for mitotic division. It is well-established that coordinated and localized changes in actin and microtubule dynamics are vital for cytokinetic ring formation, as well as establishment of the abscission site. Actin cytoskeleton reorganization during abscission would not be possible without the interplay between Rab11-and Rab35containing endosomes and their effector proteins, whose roles in regulating endocytic pathways at the cleavage furrow have now been studied extensively. Here, we identified Rab14 as novel regulator of abscission. We demonstrate that depletion of Rab14 causes either cytokinesis failure or significantly prolongs division time. We show that Rab14 regulates the efficiency of recruiting Rab11-endosomes to the central spindle microtubules and that Rab14 knockout leads to inhibition of actin clearance at the abscission site. Finally, we demonstrate that Rab14 binds to microtubule minus-end interacting MACF2/CAMSAP3 complex and that this binding is required for targeting of early endosomes to the central spindle. Collectively, our data identified Rab14/MACF2/CAMSAP3 as a protein complex that regulates Rab11-endosome targeting and the establishment of the abscission site.

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DNA damage response proteins regulating mitotic cell division: double agents preserving genome stability

Cited by 56 publications

References 159 publications

DNA Replication Stress and Chromosomal Instability: Dangerous Liaisons

DNA Replication Stress and Chromosomal Instability: Dangerous Liaisons

Rab14/MACF2 complex regulates endosomal targeting during cytokinesis

Rab14/MACF2/CAMSAP3 Complex Regulates Endosomal Targeting to the Abscission Site During Cytokinesis

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