Homologous recombination mediates cellular resistance and fraction size sensitivity to radiation therapy

Somaiah, Navita; Yarnold, John; Lagerqvist, Anne; Rothkamm, Kai; Helleday, Thomas

doi:10.1016/j.radonc.2013.05.012

Cited by 28 publications

(28 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The other study used DT40 (chicken cell lines) that mainly depend on HRR to repair DNA DSB and we used mammalian cells that depend on both NHEJ and HRR to repair DNA DSB. Our data are supported by the data obtained from another group using CHO cells (Somaiah et al 2013). …”

Section: Resultssupporting

confidence: 90%

“…There are many reports that have studied different aspects of SLDR, such as cell cycle distribution (Zaider et al 1996), later tissue response (Brenner et al 1998), p53 (a tumor suppressor) involved effects (Pekkola-Heino et al 1998); halftime for SLDR (Guerrero et al 2006); intrinsic radiosensitivity and SLDR (Guerrero et al 2006), implication (Liu et al 2011) and inhibition of SLDR (Ben-Hur et al 2012), etc. One earlier study reported that SLDR depended on HRR in chicken DT40 cells (Utsumi et al 2001) and a recent study reported that SLDR mainly depended on Ku-dependent NHEJ in CHO cells (Somaiah et al 2013). However, for mouse and human cells, the status remains unclear.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ku-dependent non-homologous end-joining as the major pathway contributes to sublethal damage repair in mammalian cells

Liu

Lee

Liu

et al. 2015

International Journal of Radiation Biology

View full text Add to dashboard Cite

Purpose Sublethal damage repair (SLDR) is a type of repair that occurs in split dose irradiated cells, which was discovered more than 50 years ago. However, due to conflicting reported data, it remains unclear which DNA double strand break (DSB) repair pathway, non-homologous end-joining (NHEJ) repair, homologous recombination repair (HRR) or both, contributes to SLDR, particularly in human cells. We were interested in clarifying this question. Methods and materials Mammalian cell lines, including human, mouse and Chinese hamster ovary (CHO) cell lines, wild type, deficient in NHEJ or HRR were irradiated with either single dose or two split doses at 2 or 4 hour intervals. The clonogenic assay was used to evaluate these cell radiosensitivities. Results All wild type or HRR deficient cells (including human, mouse and CHO cells) showed a higher survival rate after exposure to split dose versus single dose radiation, however, all classical NHEJ deficient cells (including human, mouse and hamster cells) did not show any apparent sensitivity changes between single dose and split dose irradiation. Conclusion Classical NHEJ mainly contributes to SLDR in mammalian cells (including human cells) cells. These results have the potential to improve radiotherapy.

show abstract

Section: Resultssupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Ku-dependent non-homologous end-joining as the major pathway contributes to sublethal damage repair in mammalian cells

Liu

Lee

Liu

et al. 2015

International Journal of Radiation Biology

View full text Add to dashboard Cite

show abstract

“…Recently our SLDR survival experiments not only confirmed previously published CHO cell results (Somaiah et al 2013), but also verified the results in mouse and human cells (Liu et al 2015). These results clarify that NHEJ is the major pathway for SLDR (Liu et al 2015).…”

Section: Both Sldr and Pldr Depend Mainly On Nhejsupporting

confidence: 90%

“…Different from NHEJ, HRR needs an extended template for a sister chromatin exchange and is more efficient in the S/G2 phases (Jackson et al 2009, Rothkamm et al 2003). A recent study reported that SLDR could not be observed in NHEJ deficient CHO cells (Somaiah et al 2013), suggesting that NHEJ is the major pathway for SLDR, and we used different repair deficient mouse or human cell lines to further demonstrate that SLDR depends mainly on NHEJ (Liu et al 2015). Since it remains unclear which repair pathway, NHEJ or HRR, or both contributes to PLDR (Hall et al 2010), although different groups reported that some DNA repair related factors affect the efficiency of PLDR (Arlett et al 1984, Autsavapromporn et al 2013, Boothman et al 1989, Riballo et al 2004, Veuger et al 2003, Wilson et al 1989), it is also necessary to clarify this issue.…”

Section: Introductionmentioning

confidence: 99%

DNA repair pathway choice at various conditions immediately post irradiation

Liu

Wang

Lee

et al. 2016

International Journal of Radiation Biology

View full text Add to dashboard Cite

Purpose Clarify which DNA double strand break repair pathway, non-homologous end-joining (NHEJ), homologous recombination repair (HRR) or both, plays a key role in potentially lethal damage repair (PLDR). Methods and materials Combining published data and our new potentially lethal damage repair (PLDR) data, we explain whether similar to sublethal damage repair (SLDR), PLDR also mainly depends on NHEJ versus HRR. The PLDR data were used the same cell lines: wild type, HRR or NHEJ deficient fibroblast cells, as those SLDR data published by our laboratory previously. The PLDR condition that we used was as commonly described by many other groups: the cells were collected immediately or overnight post ionizing radiation for colony formation after cultured to a plateau phase with a low concentration of serum medium. Results Enough data from other groups and our lab showed that wild type or HRR deficient cells had efficient PLDR, but NHEJ deficient cell lines did not. Conclusion NHEJ contributes more to PLDR than HRR in mammalian (including human) cells, which is similar to SLDR. Since both SLDR and PLDR are relevant to clinical tumor status while undergoing radiotherapy, such clarification may benefit radiotherapy in the near future.

show abstract

“…Mammalian fibroblasts genetically defective in NHEJ are exquisitely radiosensitive, as shown by the SCID phenotype in mice [80,81] and they are not spared by low dose rate irradiation that mimics hyperfractionation [82]. We have shown that sensitivity to fraction size is undetectable in cells lacking functional NHEJ and thereby relying on homologous recombination for repair of radiation-induced DSBs [83]. DNA-PK-deficient cells accumulate in S/G2 phase of the cell cycle with fractionated irradiation.…”

Section: Molecular Models Of Fractionation Sensitivity In Normal Tissuesmentioning

confidence: 84%

Where Do We Look for Markers of Radiotherapy Fraction Size Sensitivity?

2015

View full text Add to dashboard Cite

Homologous recombination mediates cellular resistance and fraction size sensitivity to radiation therapy

Cited by 28 publications

References 42 publications

Ku-dependent non-homologous end-joining as the major pathway contributes to sublethal damage repair in mammalian cells

Ku-dependent non-homologous end-joining as the major pathway contributes to sublethal damage repair in mammalian cells

DNA repair pathway choice at various conditions immediately post irradiation

Where Do We Look for Markers of Radiotherapy Fraction Size Sensitivity?

Contact Info

Product

Resources

About