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Identifier

000382263

Title

Η πρωτεϊνική κινάση Chk1 είναι απαραίτητη για την επιδιόρθωση των μεροτελικών προσδέσεων στην κυτταρική διαίρεση

Alternative Title

Chk1 is required for correction of merotelic attachments during mitotic cell division

Author

Πετσαλάκη, Ελένη

Thesis advisor

Παπαματθαιάκης, Ιωσήφ
Ζάχος, Γ.

Reviewer

Αθανασάκη, Ε.
Αλεξανδράκη, Δ.

Abstract

Merotelic kinetochore attachments can induce mis-segregated chromosomes in anaphase. In the present study, we show that Chk1 kinase, a component of the DNA damage and DNA replication responses, protects vertebrate cells against merotelic attachments and lagging chromosomes and regulates correction of merotelic attachments during a prolonged metaphase. Decreased Chk1 activity leads to hyperstable kinetochore-microtubules, unstable binding of MCAK, Kif2b and Mps1 to centromeres or kinetochores and reduced phosphorylation of Hec1 by Aurora-B kinase. Chk1 phosphorylates Aurora-B Serine 331 at kinetochores and this phosphorylation is high in prometaphase and decreases significantly when chromosomes bi-orient. We propose that phosphorylation of Serine 331 by Chk1 is required for localization of MCAK, Kif2b and Mps1 to centromeres or kinetochores and for Hec1 phosphorylation. Furthermore, inhibition of Mps1 activity diminishes initial recruitment of MCAK and Kif2b to centromeres or kinetochores, impairs mitotic Hec1 phosphorylation and exacerbates merotelic attachments in the absence of Chk1 function. We propose that Chk1 and Mps1 jointly regulate Aurora-B, MCAK, Kif2b and Hec1 functions to correct merotelic attachments. These results suggest a previously unreported role for Chk1 and Mps1 in error correction.

Language

Greek

Subject

Aurora-B

Merotelic

Mitosis

Mps1

Μίτωση

Μεροτελική πρόσδεση

Issue date

2014-01-29

Collection