scholarly journals Sister Chromatid Exchanges Are Mediated by Homologous Recombination in Vertebrate Cells

1999 ◽  
Vol 19 (7) ◽  
pp. 5166-5169 ◽  
Author(s):  
Eiichiro Sonoda ◽  
Masao S. Sasaki ◽  
Ciaran Morrison ◽  
Yuko Yamaguchi-Iwai ◽  
Minoru Takata ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Sister Chromatid ◽  
Sister Chromatid Exchanges ◽  
Dna Lesions ◽  
End Joining ◽  
Chromosomal Stability ◽  
Tumorigenic Potential ◽  
Associated Proteins ◽  
Chromatid Exchanges

ABSTRACT Sister chromatid exchange (SCE) frequency is a commonly used index of chromosomal stability in response to environmental or genetic mutagens. However, the mechanism generating cytologically detectable SCEs and, therefore, their prognostic value for chromosomal stability in mitotic cells remain unclear. We examined the role of the highly conserved homologous recombination (HR) pathway in SCE by measuring SCE levels in HR-defective vertebrate cells. Spontaneous and mitomycin C-induced SCE levels were significantly reduced for chicken DT40 B cells lacking the key HR genes RAD51 and RAD54but not for nonhomologous DNA end-joining (NHEJ)-defectiveKU70 −/− cells. As measured by targeted integration efficiency, reconstitution of HR activity by expression of a human RAD51 transgene restored SCE levels to normal, confirming that HR is the mechanism responsible for SCE. Our findings show that HR uses the nascent sister chromatid to repair potentially lethal DNA lesions accompanying replication, which might explain the lethality or tumorigenic potential associated with defects in HR or HR-associated proteins.

scholarly journals Sister chromatid exchanges induced by perturbed replication are formed independently of homologous recombination factors

2021 ◽  
Author(s):  
Anne Margriet Heijink ◽  
Colin Stok ◽  
David Porubsky ◽  
Eleni M. Manolika ◽  
Yannick P. Kok ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Sister Chromatid ◽  
Parp Inhibitor ◽  
Sister Chromatid Exchanges ◽  
Fragile Sites ◽  
Dna Lesions ◽  
Parp Inhibition ◽  
Dna Breaks ◽  
Brca1 Brca2 ◽  
Chromatid Exchanges

SummarySister chromatid exchanges (SCEs) are products of joint DNA molecule resolution, and are considered to form through homologous recombination (HR). Indeed, upon generation of irradiation-induced DNA breaks, SCE induction was compromised in cells deficient for canonical HR factors BRCA1, BRCA2 and RAD51. Contrarily, replication-blocking agents, including PARP inhibitors, induced SCEs independently of BRCA1, BRCA2 and RAD51. PARP inhibitor-induced SCEs were enriched at common fragile sites (CFSs), and were accompanied by post-replicative single-stranded DNA (ssDNA) gaps. Moreover, PARP inhibitor-induced replication lesions were transmitted into mitosis, suggesting that SCEs originate from mitotic processing of under-replicated DNA. We found that DNA polymerase theta (POLQ) was recruited to mitotic DNA lesions, and loss of POLQ resulted in reduced SCE numbers and severe chromosome fragmentation upon PARP inhibition in HR-deficient cells. Combined, our data show that PARP inhibition generates under-replicated DNA, which is transferred into mitosis and processed into SCEs, independently of canonical HR factors.

scholarly journals Low doses of alpha particles do not induce sister chromatid exchanges in bystander Chinese hamster cells defective in homologous recombination

DNA Repair ◽  
2008 ◽  
Vol 7 (3) ◽  
pp. 515-522 ◽  
Author(s):  
Hatsumi Nagasawa ◽  
Paul F. Wilson ◽  
David J. Chen ◽  
Larry H. Thompson ◽  
Joel S. Bedford ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Sister Chromatid ◽  
Chinese Hamster ◽  
Sister Chromatid Exchanges ◽  
Alpha Particles ◽  
Low Doses ◽  
Chinese Hamster Cells ◽  
Chromatid Exchanges

Persistence of DNA lesions and the cytological cancellation of sister chromatid exchanges

Chromosoma ◽  
1985 ◽  
Vol 92 (1) ◽  
pp. 7-10 ◽  
Author(s):  
J. B. Schvartzman ◽  
V. J. Goyanes ◽  
A. Campos ◽  
A. M. Lage ◽  
C. Veiras ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Sister Chromatid Exchanges ◽  
Dna Lesions ◽  
Chromatid Exchanges ◽  
Persistence Of Dna
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