MCPH1 is essential for cellular adaptation to the G2-phase decatenation checkpoint

María Arroyo, Ryoko Kuriyama, Israel Guerrero, Daniel Keifenheim, Ana Cañuelo, Jesús Calahorra, Antonio Sánchez, Duncan J Clarke, J. Alberto Marchal

Research output: Contribution to journalArticle

Abstract

Cellular checkpoints controlling entry into mitosis monitor the integrity of the DNA and delay mitosis onset until the alteration is fully repaired. However, this canonical response can weaken, leading to a spontaneous bypass of the checkpoint, a process referred to as checkpoint adaptation. Here, we have investigated the contribution of microcephalin 1 (MCPH1), mutated in primary microcephaly, to the decatenation checkpoint, a less-understood G2 pathway that delays entry into mitosis until chromosomes are properly disentangled. Our results demonstrate that, although MCPH1 function is dispensable for activation and maintenance of the decatenation checkpoint, it is required for the adaptive response that bypasses the topoisomerase II inhibition----mediated G2 arrest. MCPH1, however, does not confer adaptation to the G2 arrest triggered by the ataxia telangiectasia mutated- and ataxia telangiectasia and rad3 related-based DNA damage checkpoint. In addition to revealing a new role for MCPH1 in cell cycle control, our study provides new insights into the genetic requirements that allow cellular adaptation to G2 checkpoints, a process that remains poorly understood.-Arroyo, M., Kuriyama, R., Guerrero, I., Keifenheim, D., Cañuelo, A., Calahorra, J., Sánchez, A., Clarke, D. J., Marchal, J. A. MCPH1 is essential for cellular adaptation to the G2-phase decatenation checkpoint.

Original languageEnglish (US)
Pages (from-to)8363-8374
Number of pages12
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume33
Issue number7
DOIs
StatePublished - Jul 1 2019

Fingerprint

G2 Phase Cell Cycle Checkpoints
Mitosis
Ataxia Telangiectasia
Type II DNA Topoisomerase
DNA
Chromosomes
Microcephaly
Chemical activation
Cells
Cell Cycle Checkpoints
DNA Damage
Maintenance

Keywords

  • MCPH1
  • cell cycle control
  • checkpoint adaptation
  • chromosome condensation
  • topoisomerase II

PubMed: MeSH publication types

  • Journal Article

Cite this

MCPH1 is essential for cellular adaptation to the G2-phase decatenation checkpoint. / Arroyo, María; Kuriyama, Ryoko; Guerrero, Israel; Keifenheim, Daniel; Cañuelo, Ana; Calahorra, Jesús; Sánchez, Antonio; Clarke, Duncan J; Marchal, J. Alberto.

In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 33, No. 7, 01.07.2019, p. 8363-8374.

Research output: Contribution to journalArticle

Arroyo, María ; Kuriyama, Ryoko ; Guerrero, Israel ; Keifenheim, Daniel ; Cañuelo, Ana ; Calahorra, Jesús ; Sánchez, Antonio ; Clarke, Duncan J ; Marchal, J. Alberto. / MCPH1 is essential for cellular adaptation to the G2-phase decatenation checkpoint. In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019 ; Vol. 33, No. 7. pp. 8363-8374.
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AB - Cellular checkpoints controlling entry into mitosis monitor the integrity of the DNA and delay mitosis onset until the alteration is fully repaired. However, this canonical response can weaken, leading to a spontaneous bypass of the checkpoint, a process referred to as checkpoint adaptation. Here, we have investigated the contribution of microcephalin 1 (MCPH1), mutated in primary microcephaly, to the decatenation checkpoint, a less-understood G2 pathway that delays entry into mitosis until chromosomes are properly disentangled. Our results demonstrate that, although MCPH1 function is dispensable for activation and maintenance of the decatenation checkpoint, it is required for the adaptive response that bypasses the topoisomerase II inhibition----mediated G2 arrest. MCPH1, however, does not confer adaptation to the G2 arrest triggered by the ataxia telangiectasia mutated- and ataxia telangiectasia and rad3 related-based DNA damage checkpoint. In addition to revealing a new role for MCPH1 in cell cycle control, our study provides new insights into the genetic requirements that allow cellular adaptation to G2 checkpoints, a process that remains poorly understood.-Arroyo, M., Kuriyama, R., Guerrero, I., Keifenheim, D., Cañuelo, A., Calahorra, J., Sánchez, A., Clarke, D. J., Marchal, J. A. MCPH1 is essential for cellular adaptation to the G2-phase decatenation checkpoint.

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