Homologous recombination defects and how they affect replication fork maintenance

Mi Young Son; Paul Hasty; Mi Young Son; Paul Hasty

doi:10.3934/genet.2018.4.192

AIMS Genetics

2018, Volume 5, Issue 4: 192-211. doi: 10.3934/genet.2018.4.192

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Review

Homologous recombination defects and how they affect replication fork maintenance

Mi Young Son ¹,
Paul Hasty ^{1,2,3
,
,}

1.
Department of Molecular Medicine and Institute of Biotechnology, UT Health San Antonio, 15355 Lambda Drive, San Antonio, USA
2.
The Mays Cancer Center, USA
3.
Sam and Ann Barshop Institute for Longevity and Aging Studies, USA

Received: 22 January 2019 Accepted: 18 March 2019 Published: 03 April 2019

Homologous recombination (HR) repairs DNA double strand breaks (DSBs) and stabilizes replication forks (RFs). RAD51 is the recombinase for the HR pathway. To preserve genomic integrity, RAD51 forms a filament on the 3’ end of a DSB and on a single-stranded DNA (ssDNA) gap. But unregulated HR results in undesirable chromosomal rearrangements. This review describes the multiple mechanisms that regulate HR with a focus on those mechanisms that promote and contain RAD51 filaments to limit chromosomal rearrangements. If any of these pathways break down and HR becomes unregulated then disease, primarily cancer, can result.
- homologous recombination,
- replication fork stability,
- RAD51 filaments,
- genomic integrity,
- gross chromosomal rearrangements
Citation: Mi Young Son, Paul Hasty. Homologous recombination defects and how they affect replication fork maintenance[J]. AIMS Genetics, 2018, 5(4): 192-211. doi: 10.3934/genet.2018.4.192

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Abstract

Homologous recombination (HR) repairs DNA double strand breaks (DSBs) and stabilizes replication forks (RFs). RAD51 is the recombinase for the HR pathway. To preserve genomic integrity, RAD51 forms a filament on the 3’ end of a DSB and on a single-stranded DNA (ssDNA) gap. But unregulated HR results in undesirable chromosomal rearrangements. This review describes the multiple mechanisms that regulate HR with a focus on those mechanisms that promote and contain RAD51 filaments to limit chromosomal rearrangements. If any of these pathways break down and HR becomes unregulated then disease, primarily cancer, can result.

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