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Review
. 2013 Dec;41(6):1706-11.
doi: 10.1042/BST20130146.

The CINs of the centromere

Susan L Forsburg  1
Affiliations
Review

The CINs of the centromere

Susan L Forsburg. Biochem Soc Trans. 2013 Dec.

Abstract

Replication stress is a significant contributor to genome instability. Recent studies suggest that the centromere is particularly susceptible to replication stress and prone to rearrangements and genome damage, as well as chromosome loss. This effect is enhanced by loss of heterochromatin. The resulting changes in genetic organization, including chromosome loss, increased mutation and loss of heterozygosity, are important contributors to malignant growth.

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Figures

Figure 1
Figure 1
A. The fission yeast centromere, showing the structure of established heterochromatin with Swi6 binding tH3K9me. B. During early S phase, H3K9me is reduced. Swi6 binding to DDK promotes early replication initiation. Unopposed binding of Chp1 (in the absence of Swi6) opposes early initiation.
Figure 2
Figure 2
A. Minichromosome model for chromosome rearrangement [Tinline-Purvis, 2009 #5381][Nakamura, 2008 #5382] leads to isochromosome formation or acrocentric deriiatives through BIR. B. Internal model for centromere rearrangement uses an interrupted ura4+ gene to monitor recombination. C. Double mutants that disrupt Swi6 or Chp1 and components of replication fork stability have enhanced defects, using the system in Fig 2b. Median recombination rate reported. Original data and statistical analysis from [Li, 2013 #6465].
See this image and copyright information in PMC

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