title: The polymorphic hMSH5 C85T allele augments radiotherapy-induced spermatogenic impairment.
abstract: The hMSH5 C85T polymorphism (encoding hMSH5 P29S) is associated with male infertility and radiation-induced apoptotic response. To date, however, the potential association of hMSH5 C85T polymorphism with DNA damage accumulation in spermatozoa of cancer patients treated with radiotherapy is largely unknown. We investigated hMSH5 C85T allele and genotype frequencies, routine semen analysis and sperm DNA Fragmentation Index (DFI) in 113 testicular germ cell tumor (TGCT) patients before and after radiotherapy. The hMSH5 C85T allele is not associated with the occurrence of TGCT. However, in comparison with the CC genotype, TGCT patients with the CT + TT genotypes showed significantly altered sperm counts, sperm morphology and DFI after radiotherapy. Finally, the results of the DSB repair assay demonstrated that hMSH5 P29S could enhance radiotherapy-induced DNA damage by unleashing error-prone non-homologous end joining. Together, our studies indicate that the hMSH5 C85T variation could have an impact on the severity of radiotherapy-provoked long-term side effects through compromising the repair of radiation-induced DNA lesions.
authors.affiliation: Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: G
authors.initials: G
authors.lastname: Gao
authors.affiliation: Department of Tumor, The Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: L
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Tumor, The Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Molecular Biosciences, Washington State University, Pullman, WA, USA.
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.affiliation: School of Molecular Biosciences, Washington State University, Pullman, WA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Her
authors.affiliation: Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: K
authors.initials: K
authors.lastname: Xu
mesh_terms: D000328:Adult; D000483:Alleles; D018797:Cell Cycle Proteins / Q000235:genetics*; D053938:DNA Fragmentation / Q000528:radiation effects*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055101:Semen Analysis; D018239:Seminoma / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D013094:Spermatozoa / Q000528:radiation effects*; D013736:Testicular Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D055815:Young Adult
chemical_list: D018797:Cell Cycle Proteins; C118481:MSH5 protein, human
keywords: hMSH5; hMSH5 C85T; radiotherapy; single nucleotide polymorphism; testicular germ cell tumor