[Structure and evolution of the eukaryotic FANCJ-like proteins].

The FANCJ-like protein family is a class of ATP-dependent helicases that can catalytically unwind duplex DNA along the 5'-3' direction. It is involved in the processes of DNA damage repair, homologous recombination and G-quadruplex DNA unwinding, and plays a critical role in maintaining genome integrity. In this study, we systemically analyzed FNACJ-like proteins from 47 eukaryotic species and discussed their sequences diversity, origin and evolution, motif organization patterns and spatial structure differences. Four members of FNACJ-like proteins, including XPD, CHL1, RTEL1 and FANCJ, were found in eukaryotes, but some of them were seriously deficient in most fungi and some insects. For example, the Zygomycota fungi lost RTEL1, Basidiomycota and Ascomycota fungi lost RTEL1 and FANCJ, and Diptera insect lost FANCJ. FANCJ-like proteins contain canonical motor domains HD1 and HD2, and the HD1 domain further integrates with three unique domains Fe-S, Arch and Extra-D. Fe-S and Arch domains are relatively conservative in all members of the family, but the Extra-D domain is lost in XPD and differs from one another in rest members. There are 7, 10 and 2 specific motifs found from the three unique domains respectively, while 5 and 12 specific motifs are found from HD1 and HD2 domains except the conserved motifs reported previously. By analyzing the arrangement pattern of these specific motifs, we found that RTEL1 and FANCJ are more closer and share two specific motifs Vb2 and Vc in HD2 domain, which are likely related with their G-quadruplex DNA unwinding activity. The evidence of evolution showed that FACNJ-like proteins were originated from a helicase, which has a HD1 domain inserted by extra Fe-S domain and Arch domain. By three continuous gene duplication events and followed specialization, eukaryotes finally possessed the current four members of FANCJ-like proteins.

[Matrix metalloproteinase-1 gene -519A/G polymorphism and the risk of coronary heart disease in Northern Chinese Han population].

OBJECTIVE: To investigate the relationship between matrix metalloproteinase (MMP) 1 gene -519A/G polymorphism and the risk of coronary heart disease (CHD) in Northern Chinese Han population. METHODS: A total of 517 patients with CHD and 380 healthy adults diagnosed by coronary angiography were genotyped by polymerase chain reaction-restriction fragment length polymorphism and DNA sequence technology for the -519A/G polymorphism in MMP1 gene. RESULTS: (1) The frequency of AA genotype was significantly higher in patients with CHD than that in controls [67.70% (350/517) vs. 40.26% (153/380), OR = 1.64, P < 0.001, 95%CI: 1.44 - 1.86]. People carrying A allele had increased risk for CHD (OR = 1.49, P < 0.001, 95%CI: 1.33 - 1.69). (2) The frequency of AA genotype was higher in patients with acute coronary syndrome (ACS) than patients with stable angina pectoris [68.81% (278/404) vs. 51.76% (44/85), P < 0.01, 95%CI: 1.04 - 1.27]. The A allele carriers were more likely to develop ACS (OR = 1.11, 95%CI: 1.01 - 1.21, P < 0.05). CONCLUSION: Our data shows MMP1 gene -519A/G polymorphism is associated with the risk of CHD, and A allele carriers are more susceptible for CHD in Northern Chinese Han population.