scholarly journals Bcl6 Is Required for Somatic Hypermutation and Gene Conversion in Chicken DT40 Cells

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0149146 ◽  
Author(s):  
Alan M. Williams ◽  
Yaakov Maman ◽  
Jukka Alinikula ◽  
David G. Schatz
Keyword(s):  
Gene Conversion ◽  
Somatic Hypermutation ◽  
Dt40 Cells

scholarly journals Role for RAD18 in Homologous Recombination in DT40 Cells

2006 ◽  
Vol 26 (21) ◽  
pp. 8032-8041 ◽  
Author(s):  
Dávid Szüts ◽  
Laura J. Simpson ◽  
Sarah Kabani ◽  
Mitsuyoshi Yamazoe ◽  
Julian E. Sale
Keyword(s):  
Dna Damage ◽  
Homologous Recombination ◽  
Gene Conversion ◽  
Early Stage ◽  
Current Evidence ◽  
Recombination Reaction ◽  
Immunoglobulin Gene ◽  
Postreplication Repair ◽  
Strand Breaks ◽  
Dt40 Cells

ABSTRACT RAD18 is an E3 ubiquitin ligase that catalyzes the monoubiquitination of PCNA, a modification central to DNA damage bypass and postreplication repair in both yeast and vertebrates. Although current evidence suggests that homologous recombination provides an essential backup in vertebrate rad18 mutants, we show that in chicken DT40 cells this is not the case and that RAD18 plays a role in the recombination reaction itself. Gene conversion tracts in the immunoglobulin locus of rad18 cells are shorter and are associated with an increased frequency of deletions and duplications. rad18 cells also exhibit reduced efficiency of gene conversion induced by targeted double-strand breaks in a reporter construct. Blocking an early stage of the recombination reaction by disruption of XRCC3 not only suppresses immunoglobulin gene conversion but also prevents the aberrant immunoglobulin gene rearrangements associated with RAD18 deficiency, reverses the elevated sister chromatid exchange of the rad18 mutant, and reduces its sensitivity to DNA damage. Together, these data suggest that homologous recombination is toxic in the absence of RAD18 and show that, in addition to its established role in postreplication repair, RAD18 is also required for the orderly completion of gene conversion.

scholarly journals Brca1 in immunoglobulin gene conversion and somatic hypermutation

DNA Repair ◽  
2008 ◽  
Vol 7 (2) ◽  
pp. 253-266 ◽  
Author(s):  
Simonne Longerich ◽  
Brian J. Orelli ◽  
Richard W. Martin ◽  
Douglas K. Bishop ◽  
Ursula Storb
Keyword(s):  
Gene Conversion ◽  
Somatic Hypermutation ◽  
Immunoglobulin Gene

scholarly journals AID Mediates Hypermutation by Deaminating Single Stranded DNA

2003 ◽  
Vol 197 (10) ◽  
pp. 1291-1296 ◽  
Author(s):  
Sarah K. Dickerson ◽  
Eleonora Market ◽  
Eva Besmer ◽  
F. Nina Papavasiliou
Keyword(s):  
Gene Conversion ◽  
Somatic Hypermutation ◽  
Class Switch Recombination ◽  
Functional Link ◽  
Single Stranded Dna ◽  
Class Switch ◽  
Mutational Hotspots ◽  
Activation Induced Deaminase ◽  
Precise Role

Activation-induced deaminase (AID) is a protein indispensable for the diversification of immunoglobulin (Ig) genes by somatic hypermutation (SHM), class switch recombination (CSR), and gene conversion. To date, the precise role of AID in these processes has not been determined. Here we demonstrate that purified, tetrameric AID can deaminate cytidine residues in DNA, but not in RNA. Furthermore, we show that AID will bind and deaminate only single-stranded DNA, which implies a direct, functional link between hypermutation and transcription. Finally, AID does not target mutational hotspots, thus mutational targeting to specific residues must be attributed to different factors.

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