TY - JOUR
T1 - Regulation of homologous recombination in eukaryotes
AU - Heyer, Wolf Dietrich
AU - Ehmsen, Kirk T.
AU - Liu, Jie
PY - 2010/12/1
Y1 - 2010/12/1
N2 - Homologous recombination (HR) is required for accurate chromosome segregation during the first meiotic division and constitutes a key repair and tolerance pathway for complex DNA damage, including DNA double-strand breaks, interstrand crosslinks, and DNA gaps. In addition, recombination and replication are inextricably linked, as recombination recovers stalled and broken replication forks, enabling the evolution of larger genomesreplicons. Defects in recombination lead to genomic instability and elevated cancer predisposition, demonstrating a clear cellular need for recombination. However, recombination can also lead to genome rearrangements. Unrestrained recombination causes undesired endpoints (translocation, deletion, inversion) and the accumulation of toxic recombination intermediates. Evidently, HR must be carefully regulated to match specific cellular needs. Here, we review the factors and mechanistic stages of recombination that are subject to regulation and suggest that recombination achieves flexibility and robustness by proceeding through metastable, reversible intermediates.
AB - Homologous recombination (HR) is required for accurate chromosome segregation during the first meiotic division and constitutes a key repair and tolerance pathway for complex DNA damage, including DNA double-strand breaks, interstrand crosslinks, and DNA gaps. In addition, recombination and replication are inextricably linked, as recombination recovers stalled and broken replication forks, enabling the evolution of larger genomesreplicons. Defects in recombination lead to genomic instability and elevated cancer predisposition, demonstrating a clear cellular need for recombination. However, recombination can also lead to genome rearrangements. Unrestrained recombination causes undesired endpoints (translocation, deletion, inversion) and the accumulation of toxic recombination intermediates. Evidently, HR must be carefully regulated to match specific cellular needs. Here, we review the factors and mechanistic stages of recombination that are subject to regulation and suggest that recombination achieves flexibility and robustness by proceeding through metastable, reversible intermediates.
KW - Cyclin-dependent kinase
KW - DNA damage response (DDR)
KW - DNA repair
KW - phosphorylation
KW - sumoylation
KW - ubiquitylation
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U2 - 10.1146/annurev-genet-051710-150955
DO - 10.1146/annurev-genet-051710-150955
M3 - Article
C2 - 20690856
AN - SCOPUS:78149425175
VL - 44
SP - 113
EP - 139
JO - Annual Review of Genetics
JF - Annual Review of Genetics
SN - 0066-4197
ER -