Synaptonemal complex proteins modulate the level of genome integrity in cancers

Abstract

The synaptonemal complex (SC) is a proteinaceous structure that is transiently formed during meiosis to promote homologous recombination between maternal and paternal chromosomes. As this structure is required only for meiotic recombination, the proteins constituting the complex are almost undetectable in normal somatic cells, but they can be expressed under the conditions in which the transcriptional machinery is deregulated. Accumulating evidence indicates that they are epigenetically expressed in cancers of various origin. Not surprisingly, in contrast to their meiotic roles, the somatic roles of the SC proteins remain to be investigated. However, it has recently been reported that SYCP3 and SYCE2 control DNA double‐strand break repair negatively and positively, respectively, suggesting that the ectopic expression of the SC proteins in somatic cells could be associated with the maintenance of genomic instability. Thus, it is highly likely that the investigation of the somatic roles of the SC proteins would improve our understanding of the mechanisms underlying tumor development.

Role and Clinical Utility of Cancer/Testis Antigens in Head and Neck Squamous Cell Carcinoma

“…SYCP2 expression was detected in HPV16 positive but not negative keratinocyte lines and expression was promoted synergistically by HPV16 E6 and E7 [140]. As mentioned previously, synaptonemal complex components SYCP1, SYCP2, SYCP3, SYCE1, and SYCE2 are expressed in cancers [147].…”

“…As mentioned previously, the Synaptonemal complex protein 2 (SYCP2) protein is a component of the synaptonemal complex, which joins homologous chromosomes prior to meiotic recombination [146]. The synaptonemal complex consists of two axial/lateral elements, a central element, and transverse filaments [147]. During the first stage of meiotic prophase I, called leptotene, chromosomes condense, and the sister chromatids organize along the axial elements.…”

“…Expression of synaptonemal complex axial/lateral element SYCP3 [147] in somatic cells impairs the RAD51-mediated homologous recombination pathway, enhances sensitivity to DNA damaging agents or poly(ADP-ribose) polymerase (PARP) inhibition, and promotes chromosomal instability.…”

Guardians of the Genome: BRCA2 and Its Partners

“…In meiosis, BRCA2, RAD51, and DMC1 show punctate foci on SYCP3-marked axial elements [91][92][93]. Normal expression of SYCP3 is limited to meiotic cells, but emerging evidence shows an abnormal expression of SYCP3 in many cancers [169]. Like MEILB2-BRME1, the ectopic expression of SYCP3 in somatic cells has a negative effect on HR repair.…”

Prevalence of HPV in Mexican Patients with Head and Neck Squamous Carcinoma and Identification of Potential Prognostic Biomarkers

“…The presence of HPV in HNSCC varies with the anatomical site; that is to say, it has been found in 48.5% of OPSCC, 24% of cancers of the oral cavity (OCSCC), and 22% of those in the larynx (LASCC) [9]. The most frequent viral genotype in HNSCC is HPV16, followed by HPV 18,33,35,52,45, and 39 [10].…”