Editing Spermatocyte (section)

===Damage, repair, and failure===
Spermatocytes regularly overcome double-strand breaks and other [[DNA damage (naturally occurring)|DNA damages]] in the prophase stage of [[meiosis]]. These damages can arise by the programmed activity of [[Spo11]], an enzyme employed in meiotic recombination, as well as by un-programmed breakages in DNA, such as those caused by [[oxidative stress|oxidative free radicals]] produced as products of normal metabolism. These damages are repaired by homologous recombination pathways and utilize [[RAD1 homolog|RAD1]] and γ[[H2AX]], which recognize double strand breaks and modify [[chromatin]], respectively. As a result, double strand breaks in meiotic cells, unlike mitotic cells, do not typically lead to [[apoptosis]], or cell death.<ref name="DNA damage">{{cite journal |vauthors=Matulis S, Handel MA |title=Spermatocyte responses in vitro to induced DNA damage |journal=Molecular Reproduction and Development |volume=73 |issue=8 |pages=1061–72 |date=August 2006  |pmid=16700071 |doi=10.1002/mrd.20508|s2cid=21185220 }}</ref> [[Homologous recombination]]al repair (HRR) of double-strand breaks occurs in mice during sequential stages of [[spermatogenesis]] but is most prominent in spermatocytes.<ref name="pmid16989005">{{cite journal |vauthors=Srivastava N, Raman MJ |title=Homologous recombination-mediated double-strand break repair in mouse testicular extracts and comparison with different germ cell stages |journal=Cell Biochem. Funct. |volume=25 |issue=1 |pages=75–86 |year=2007 |pmid=16989005 |doi=10.1002/cbf.1375 |s2cid=24830710 }}</ref> In spermatocytes, HRR events occur mainly in the pachytene stage of meiosis and the [[gene conversion]] type of HRR is predominant, whereas in other stages of spermatogenesis the reciprocal exchange type of HRR is more frequent.<ref name="pmid16989005" /> During mouse spermatogenesis, the [[mutation]] frequencies of cells at the different stages, including pachytene spermatocytes, are 5 to 10-fold lower than the mutation frequencies in [[somatic cell]]s.<ref name="pmid9707592">{{cite journal |vauthors=Walter CA, Intano GW, McCarrey JR, McMahan CA, Walter RB |title=Mutation frequency declines during spermatogenesis in young mice but increases in old mice |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue=17 |pages=10015–9 |year=1998 |pmid=9707592 |pmc=21453 |doi= 10.1073/pnas.95.17.10015|bibcode=1998PNAS...9510015W |doi-access=free }}</ref> Because of their elevated [[DNA repair]] capability, spermatocytes likely play a central role in the maintenance of these lower mutation rates, and thus in the preservation of the genetic integrity of the male germ line.

It is known that [[heterozygous]] chromosomal rearrangements lead to spermatogenic disturbance or failure; however the molecular mechanisms that cause this are not as well known. It is suggested that a passive mechanism involving asynaptic region clustering in spermatocytes is a possible cause. Asynaptic regions are associated with [[BRCA1]], kinase [[Ataxia telangiectasia and Rad3 related|ATR]] and γ[[H2AX]] presence in [[pachytene]] spermatocytes.<ref name="Spermato failure">{{cite journal |vauthors=Sciurano RB, Rahn MI, Rey-Valzacchi G, Coco R, Solari AJ |title=The role of asynapsis in human spermatocyte failure |journal=International Journal of Andrology |volume=35 |issue=4 |pages=541–9 |date=August 2012  |pmid=21977946 |doi=10.1111/j.1365-2605.2011.01221.x|doi-access=free }}</ref>