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The MRN-CtIP pathway is required for metaphase chromosome alignment.

Abstract：

:Faithful duplication of the genome in S phase followed by its accurate segregation in mitosis is essential to maintain genomic integrity. Recent studies have suggested that proteins involved in DNA transactions are also required for whole-chromosome stability. Here we demonstrate that the MRN (Mre11, Rad50, and Nbs1) complex and CtIP are required for accurate chromosome segregation. Depletion of Mre11 or CtIP, antibody-mediated inhibition of Mre11, or small-molecule inhibition of MRN using mirin results in metaphase chromosome alignment defects in Xenopus egg extracts. Similarly, loss of MRN function adversely affects spindle assembly around DNA-coated beads in egg extracts. Inhibition of MRN function in mammalian cells triggers a metaphase delay and disrupts the RCC1-dependent RanGTP gradient. Addition of the Mre11 inhibitor mirin to egg extracts and mammalian cells reduces RCC1 association with mitotic chromosomes. Thus, the MRN-CtIP pathway contributes to Ran-dependent mitotic spindle assembly by modulating RCC1 chromosome association.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Rozier L,Guo Y,Peterson S,Sato M,Baer R,Gautier J,Mao Y

doi

10.1016/j.molcel.2013.01.023

subject

Has Abstract

pub_date

2013-03-28 00:00:00

pages

1097-107

issue

6

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(13)00087-7

journal_volume

49

pub_type

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