The replication protein A complex (RPA) plays a crucial role in DNA replication and damage response. However, it is not known whether this complex is regulated by the SUMOylation pathway. Here we show that the 70kd subunit of RPA (RPA70) associates with a Sentrin/SUMO-specific protease, SENP6, in the nucleus to maintain RPA70 in a hypo-SUMOylated state during S phase. Campothecin (CPT), an inducer of replication stress, dissociates SENP6 from RPA70 allowing RPA70 to be modified by a small ubiquitin-like modifier 2/3 (SUMO-2/3). RPA70 SUMOylation facilitates recruitment of Rad51 to the DNA damage foci to initiate DNA repair through homologous recombination (HR). Cell lines that expressed a RPA70 mutant that cannot be SUMOylated are defective in HR and have a marked increase in sensitivity to CPT. These results demonstrate that SUMOylation status of RPA70 plays a critical role in the regulation of DNA repair through homologous recombination.

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Lutein and zeaxanthin are thought to decrease the incidence of age-related macular degeneration (AMD); however, findings have been inconsistent. We conducted a systematic literature review and meta-analysis to evaluate the relationship between dietary intake of lutein and zeaxanthin and AMD risk. Relevant studies were identified by searching five databases up to April 2010. Reference lists of articles were retrieved, and experts were contacted. Literature search, data extraction and study quality assessment were performed independently by two reviewers and results were pooled quantitatively using meta-analysis methods. The potential sources of heterogeneity and publication bias were also estimated. The search yielded six longitudinal cohort studies. The pooled relative risk (RR) for early AMD, comparing the highest with the lowest category of lutein and zeaxanthin intake, was 0·96 (95 % CI 0·78, 1·17). Dietary intake of these carotenoids was significantly related with a reduction in risk of late AMD (RR 0·74; 95 % CI 0·57, 0·97); and a statistically significant inverse association was observed between lutein and zeaxanthin intake and neovascular AMD risk (RR 0·68; 95 % CI 0·51, 0·92). The results were essentially consistent among subgroups stratified by participant characteristics. The findings of the present meta-analysis indicate that dietary lutein and zeaxanthin is not significantly associated with a reduced risk of early AMD, whereas an increase in the intake of these carotenoids may be protective against late AMD. However, additional studies are needed to confirm these relationships.Key words: Lutein: Zeaxanthin: Age-related macular degeneration: Meta-analysis Age-related macular degeneration (AMD), the leading cause of legal blindness in people aged over 65 years in industrialised countries, is a progressive disorder primarily affecting the macula, the central region of the retina involved with central vision (1) . Early AMD is characterised clinically by yellowish deposits known as soft drusen accumulations and pigmentary abnormalities in the retinal pigment epithelium (RPE) and Bruch's membrane, whereas late-stage manifestations encompass atrophy of photoreceptors and the RPE underlying it, choroidal neovascularisation, subretinal haemorrhage, detachment of RPE and retinal scarring (2) . Currently, it has been reported that more than ten million people in the USA and approximately fifty million worldwide suffer from AMD (3) . In the UK, almost 200 000 people aged 75 years or older were visually impaired due to AMD (4) .Owing to the sharp rise in the elderly population, the disease has brought a huge burden for the health care system and had a profound impact on the quality of life and independence of older individuals. It is estimated that by the year 2020 the number of patients with late AMD will be increased by more than 50 % to almost three million in the USA alone (5) .

Inflammatory process, characterized by microglial activation and Müller cells dysfunction, was implicated in STZ-induced diabetic retinopathy. Baicalein treatment ameliorated inflammatory process, and therefore inhibited vascular abnormality and neuron loss in diabetic retinas.

SUMMARY Small ubiquitin-like modifier (SUMO) modification has emerged as an important regulatory mechanism during embryonic development. However, it is not known whether SUMOylation plays a role in the development of the immune system. Here, we show that SUMO-specific protease 1 (SENP1) is essential for the development of early T and B cells. STAT5, a key regulator of lymphoid development, is modified by SUMO-2 and is specifically regulated by SENP1. In the absence of SENP1, SUMO-2 modified STAT5 accumulates in early lymphoid precursors, resulting in a block in its acetylation and subsequent signaling. These results demonstrate a crucial role of SENP1 in the regulation of STAT5 activation during early lymphoid development.