Genetic Exchange Between Homeologous Sequences in Mammalian Chromosomes is Averted by Local Homology Requirements for Initiation and Resolution of Recombination

Overview

Journal Genetics

Publisher Oxford University Press

Specialty Genetics

Date 2006 Jul 4

PMID 16816418

Citations 6

Authors

Derek Yang

Edie B Goldsmith

Yunfu Lin

Barbara Criscuolo Waldman

Vimala Kaza

Alan S Waldman

Affiliations

Soon will be listed here.

Abstract

We examined the mechanism by which recombination between imperfectly matched sequences (homeologous recombination) is suppressed in mammalian chromosomes. DNA substrates were constructed, each containing a thymidine kinase (tk) gene disrupted by insertion of an XhoI linker and referred to as a "recipient" gene. Each substrate also contained one of several "donor" tk sequences that could potentially correct the recipient gene via recombination. Each donor sequence either was perfectly homologous to the recipient gene or contained homeologous sequence sharing only 80% identity with the recipient gene. Mouse Ltk(-) fibroblasts were stably transfected with the various substrates and tk(+) segregants produced via intrachromosomal recombination were recovered. We observed exclusion of homeologous sequence from gene conversion tracts when homeologous sequence was positioned adjacent to homologous sequence in the donor but not when homeologous sequence was surrounded by homology in the donor. Our results support a model in which homeologous recombination in mammalian chromosomes is suppressed by a nondestructive dismantling of mismatched heteroduplex DNA (hDNA) intermediates. We suggest that mammalian cells do not dismantle mismatched hDNA by responding to mismatches in hDNA per se but rather rejection of mismatched hDNA appears to be driven by a requirement for localized homology for resolution of recombination.

Citing Articles

The Rate and Tract Length of Gene Conversion between Duplicated Genes.

Mansai S, Kado T, Innan H Genes (Basel). 2014; 2(2):313-31.

PMID: 24710193 PMC: 3924818. DOI: 10.3390/genes2020313.

Induction of recombination between diverged sequences in a mammalian genome by a double-strand break.

Bhattacharjee V, Lin Y, Waldman B, Waldman A Cell Mol Life Sci. 2013; 71(12):2359-71.

PMID: 24257896 PMC: 11113419. DOI: 10.1007/s00018-013-1520-0.

Mechanisms of ectopic gene conversion.

Hastings P Genes (Basel). 2013; 1(3):427-39.

PMID: 24000309 PMC: 3758752. DOI: 10.3390/genes1030427.

Genomic complexity of the variable region-containing chitin-binding proteins in amphioxus.

Dishaw L, Mueller M, Gwatney N, Cannon J, Haire R, Litman R BMC Genet. 2008; 9:78.

PMID: 19046437 PMC: 2632668. DOI: 10.1186/1471-2156-9-78.

Accurate homologous recombination is a prominent double-strand break repair pathway in mammalian chromosomes and is modulated by mismatch repair protein Msh2.

Smith J, Bannister L, Bhattacharjee V, Wang Y, Waldman B, Waldman A Mol Cell Biol. 2007; 27(22):7816-27.

PMID: 17846123 PMC: 2169143. DOI: 10.1128/MCB.00455-07.

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